657 results on '"lncRNA"'
Search Results
2. Differences between uncapping and removal behaviors in Apis cerana from the perspective of long non-coding RNAs
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Xiao Li, Xiaoxiao Yang, Fangdong You, Chunhui Miao, Meng Li, Kang Wang, Qingsheng Niu, Ting Ji, Zhi Wang, and Zheguang Lin
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Honeybee ,Apis cerana ,Antenna ,lncRNA ,Hygienic behavior ,Uncapping ,Biotechnology ,TP248.13-248.65 ,Genetics ,QH426-470 - Abstract
Abstract Background Hygienic behavior, a specialized form of immune response evolved in social insects, plays a crucial role in safeguarding colonies from disease spread. In honeybee colonies, such behavior typically entails the dual steps of uncapping and removal of unhealthy and deceased brood. Although in recent years, numerous studies have examined the development of hygienic behavior, the mechanisms underlying the division in the performance of uncapping and removal have yet to be sufficiently elucidated. In this regard, long non-coding RNAs (lncRNAs) have been evidenced to be engaged in regulating the physiological activities of honeybees; however, whether lncRNAs are likewise involved in the uncapping and removal tasks has not been clarified. Results In this study, the strong hygienic Apis cerana worker bees were used and the processes of uncapping and removal behaviors in three colonies were assayed with freeze-killed brood in the field. We then sequenced the antennal RNAs of honeybees to identify differentially expressed lncRNAs and performed lncRNA-mRNA association analysis to establish the differences between uncapping and removal. We detected 1,323 differentially expressed lncRNAs in the antennae, and the findings of lncRNA-mRNA association analyses revealed that the target genes of differentially expressed lncRNAs between uncapping and removal worker bees were predominantly linked to response to stimulus, receptor activity, and synapse. Notably, among the lncRNAs enriched in cellular response to stimulus, XR_001766094.2 was exclusively expressed in the uncapping worker bees. Based on these findings, we hypothesize that XR_001766094.2 plays a key role in distinguishing uncapping from removal behaviors by responding to external stimulus, thereby suggesting that the division of hygienic behaviors is governed by differential thresholds of responsiveness to environmental cues. Conclusion We characterized differences in the uncapping and removal behaviors of worker bees from a perspective of lncRNAs. Uncapping bees may be equipped with a more rapid stimulatory response and more acute olfactory sensitivity, contributing to the rapid hygienic behavior in honeybee colonies. Our results thus establish a foundation for potential lncRNA-mediated gene expression regulation in hygienic behavior.
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- 2024
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3. Characterization of lncRNA and mRNA profiles in the process of repairing peripheral nerve defects with cell-matrixed nerve grafts
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Shanshan Wang, Wei Wang, Hongkui Wang, Yimei Yang, Xingyu Liu, Ye Zhu, Xiyang Cheng, Jingfei Zhong, and Meiyuan Li
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Transcriptome ,WGCNA ,lncRNA ,Decellularized extracellular matrix ,Peripheral nerve regeneration ,Biotechnology ,TP248.13-248.65 ,Genetics ,QH426-470 - Abstract
Abstract Background Decellularized extracellular matrix (dECM) is an intriguing natural biomaterial that has garnered significant attention due to its remarkable biological properties. In our study, we employed a cell-matrixed nerve graft for the repair of sciatic nerve defects in rats. The efficacy of this approach was assessed, and concurrently, the underlying molecular regulatory mechanisms were explored to elucidate how such grafts facilitate nerve regeneration. Long noncoding RNAs (lncRNAs) regulate mRNA expression via multiple mechanisms, including post-transcriptional regulation, transcription factor effects, and competitive binding with miRNAs. These interactions between lncRNAs and mRNAs facilitate precise control of gene expression, allowing organisms to adapt to varying biological environments and physiological states. By investigating the expression profiles and interaction dynamics of mRNAs and lncRNAs, we can enhance our understanding of the molecular mechanisms through which cell-matrixed nerve grafts influence neural repair. Such studies are pivotal in uncovering the intricate networks of gene regulation that underpin this process. Results Weighted gene co-expression network analysis (WGCNA) utilizes clustering algorithms, such as hierarchical clustering, to aggregate genes with similar expression profiles into modules. These modules, which potentially correspond to distinct biological functions or processes, can subsequently be analyzed for their association with external sample traits. By correlating gene modules with specific conditions, such as disease states or responses to treatments, WGCNA enables a deeper understanding of the genetic architecture underlying various phenotypic traits and their functional implications. We identified seven mRNA modules and five lncRNA modules that exhibited associations with treatment or time-related events by WGCNA. We found the blue (mRNAs) module which displayed a remarkable enrichment in “axonal guidance” and “metabolic pathways”, exhibited strong co-expression with multiple lncRNA modules, including blue (related to “GnRH secretion” and “pyrimidine metabolism”), green (related to “arginine and proline metabolism”), black (related to “nitrogen metabolism”), grey60 (related to “PPAR signaling pathway”), and greenyellow (related to “steroid hormone biosynthesis”). All of the top 50 mRNAs and lncRNAs exhibiting the strongest correlation were derived from the blue module. Validation of key molecules were performed using immunohistochemistry and qRT-PCR. Conclusion Revealing the principles and molecular regulatory mechanisms of the interaction between materials and biological entities, such as cells and tissues, is a direction for the development of biomimetic tissue engineering technologies and clinically effective products.
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- 2024
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4. LINC01197 inhibits influenza A virus replication by serving as a PABPC1 decoy
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Yihe Wang, Ning Shi, Hansi Zhang, Jinna Luo, Hongjian Yan, Huiyan Hou, Zhenhong Guan, Lili Zhao, and Ming Duan
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Influenza A virus ,LncRNA ,LINC01197 ,replication ,Veterinary medicine ,SF600-1100 - Abstract
Abstract Influenza A viruses (IAVs) significantly impact animal and human health due to their zoonotic potential. A growing body of evidence indicates that the host’s long noncoding RNAs (lncRNAs) play crucial roles in regulating host–virus interactions during IAV infection. However, numerous lncRNAs associated with IAV infection have not been well characterised. Here, in this study, we identify the LINC01197 as an antiviral host factor. LINC01197 was significantly upregulated after IAV infection, which is controlled by the NF-κB pathway. Functional analysis revealed that overexpression of LINC01197 inhibited IAV replication and virus production, while knockdown of LINC01197 facilitated IAV replication. Mechanistically, LINC01197 directly interacts with poly(A) binding protein cytoplasmic 1 (PABPC1), which in turn sequesters and restricts its functions. This work shows that LINC01197 acts as a protein decoy, suppressing IAV replication and playing a key role in controlling IAV replication.
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- 2024
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5. LINC01089 in cancer: multifunctional roles and therapeutic implications
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Qiang Yi, Gangfeng Zhu, Xinting Ouyang, Weijian Zhu, Kui Zhong, Zheng Chen, and Jinghua Zhong
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LncRNA ,LINC01089 ,Malignant cancers ,Biological ,Clinical therapies ,Medicine - Abstract
Abstract LINC01089 is a prime example of a long non-coding RNA that plays a pivotal role in the progression of human cancers. The gene encoding this lncRNA is located on 12q24.31. LINC01089 has been demonstrated to exert tumor-suppressive effects in various cancers, including colorectal cancer, gastric cancer, lung cancer, ovarian cancer, cervical cancer, papillary thyroid carcinoma, breast cancer, and osteosarcoma. However, its role in hepatocellular carcinoma shows significant discrepancies across different studies. In this review, we systematically explore the functions of LINC01089 in human cancers through bioinformatics analysis, clinical studies, animal models, and fundamental experimental research. Furthermore, we delve into the biological mechanisms and functions of LINC01089, and discuss its potential as a future biomarker and therapeutic target in detail.
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- 2024
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6. Modelling cell type-specific lncRNA regulatory network in autism with Cycle
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Chenchen Xiong, Mingfang Zhang, Haolin Yang, Xuemei Wei, Chunwen Zhao, and Junpeng Zhang
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Autism spectrum disorder ,LncRNA ,MRNA ,LncRNA regulation ,Single-cell RNA sequencing ,Computer applications to medicine. Medical informatics ,R858-859.7 ,Biology (General) ,QH301-705.5 - Abstract
Abstract Background Autism spectrum disorder (ASD) is a class of complex neurodevelopment disorders with high genetic heterogeneity. Long non-coding RNAs (lncRNAs) are vital regulators that perform specific functions within diverse cell types and play pivotal roles in neurological diseases including ASD. Therefore, exploring lncRNA regulation would contribute to deciphering ASD molecular mechanisms. Existing computational methods utilize bulk transcriptomics data to identify lncRNA regulation in all of samples, which could reveal the commonalities of lncRNA regulation in ASD, but ignore the specificity of lncRNA regulation across various cell types. Results Here, we present Cycle (Cell type-specific lncRNA regulatory network) to construct the landscape of cell type-specific lncRNA regulation in ASD. We have found that each ASD cell type is unique in lncRNA regulation, and more than one-third and all cell type-specific lncRNA regulatory networks are characterized as scale-free and small-world, respectively. Across 17 ASD cell types, we have discovered 19 rewired and 11 stable modules, along with eight rewired and three stable hubs within the constructed cell type-specific lncRNA regulatory networks. Enrichment analysis reveals that the discovered rewired and stable modules and hubs are closely related to ASD. Furthermore, more similar ASD cell types tend to be connected with higher strength in the constructed cell similarity network. Finally, the comparison results demonstrate that Cycle is a potential method for uncovering cell type-specific lncRNA regulation. Conclusion Overall, these results illustrate that Cycle is a promising method to model the landscape of cell type-specific lncRNA regulation, and provides insights into understanding the heterogeneity of lncRNA regulation between various ASD cell types.
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- 2024
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7. As a novel prognostic model for breast cancer, the identification and validation of telomere-related long noncoding RNA signatures
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Wei Zhao, Beibei Li, Mingxiang Zhang, Peiyao Zhou, and Yongyun Zhu
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Breast cancer ,Telomere ,lncRNA ,Prognosis ,TME ,Immunotherapy ,Surgery ,RD1-811 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Telomeres are a critical component of chromosome integrity and are essential to the development of cancer and cellular senescence. The regulation of breast cancer by telomere-associated lncRNAs is not fully known, though. The goals of this study were to describe predictive telomere-related LncRNAs (TRL) in breast cancer and look into any possible biological roles for these RNAs. Methods We obtained RNA-seq data, pertinent clinical data, and a list of telomere-associated genes from the cancer genome atlas and telomere gene database, respectively. We subjected differentially expressed TRLs to co-expression analysis and univariate Cox analysis to identify a prognostic TRL. Using LASSO regression analysis, we built a prognostic model with 14 TRLs. The accuracy of the model’s prognostic predictions was evaluated through the utilization of Kaplan-Meier (K-M) analysis as well as receiver operating characteristic (ROC) curve analysis. Additionally, immunological infiltration and immune drug prediction were done using this model. Patients with breast cancer were divided into two subgroups using cluster analysis, with the latter analyzed further for variations in response to immunotherapy, immune infiltration, and overall survival, and finally, the expression of 14-LncRNAs was validated by RT-PCR. Results We developed a risk model for the 14-TRL, and we used ROC curves to demonstrate how accurate the model is. The model may be a standalone prognostic predictor for patients with breast cancer, according to COX regression analysis. The immune infiltration and immunotherapy results indicated that the high-risk group had a low level of PD-1 sensitivity and a high number of macrophages infiltrating. In addition, we’ve discovered a number of small-molecule medicines with considerable for use in treating high-risk groups. The cluster 2 subtype showed the highest immune infiltration, the highest immune checkpoint expression, and the worst prognosis among the two subtypes defined by cluster analysis, which requires more attention and treatment. Conclusion As a possible biomarker, the proposed 14-TRL signature could be utilized to evaluate clinical outcomes and treatment efficacy in breast cancer patients.
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- 2024
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8. Bone marrow mesenchymal stem cells expressing Neat-1, Hotair-1, miR-21, miR-644, and miR-144 subsided cyclophosphamide-induced ovarian insufficiency by remodeling the IGF-1–kisspeptin system, ovarian apoptosis, and angiogenesis
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Amany I. Ahmed, Mohamed F. Dowidar, Asmaa F. Negm, Hussein Abdellatif, Asma Alanazi, Mohammed Alassiri, Walaa Samy, Dina Mohamed Mekawy, Eman M. A. Abdelghany, Nesma I. El-Naseery, Mohamed A. Ibrahem, Emad Ali Albadawi, Wed Salah, Mamdouh Eldesoqui, Emil Tîrziu, Iulia Maria Bucur, Ahmed Hamed Arisha, and Tarek Khamis
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lncRNA ,microRNAs ,Premature ovarian failure ,Cyclophosphamide ,BM-MSCs ,HPG ,Gynecology and obstetrics ,RG1-991 - Abstract
Abstract Ovarian insufficiency is one of the common reproductive disorders affecting women with limited therapeutic aids. Mesenchymal stem cells have been investigated in such disorders before yet, the exact mechanism of MSCs in ovarian regeneration regarding their epigenetic regulation remains elusive. The current study is to investigate the role of the bone marrow-derived mesenchymal stem cells (BM-MSCs) lncRNA (Neat-1 and Hotair1) and miRNA (mir-21-5p, mir-144-5p, and mir-664-5p) in mitigating ovarian granulosa cell apoptosis as well as searching BM-MSCs in altering the expression of ovarian and hypothalamic IGF-1 – kisspeptin system in connection to HPG axis in a cyclophosphamide-induced ovarian failure rat model. Sixty mature female Sprague Dawley rats were divided into 3 equal groups; control group, premature ovarian insufficiency (POI) group, and POI + BM-MSCs. POI female rat model was established with cyclophosphamide. The result revealed that BM-MSCs and their conditioned media displayed a significant expression level of Neat-1, Hotair-1, mir-21-5p, mir-144-5p, and mir-664-5p. Moreover, BM-MSCs transplantation in POI rats improves; the ovarian and hypothalamic IGF-1 – kisspeptin, HPG axis, ovarian granulosa cell apoptosis, steroidogenesis, angiogenesis, energy balance, and oxidative stress. BM-MSCs expressed higher levels of antiapoptotic lncRNAs and microRNAs that mitigate ovarian insufficiency.
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- 2024
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9. Long non-coding ribonucleic acid SNHG18 induced human granulosa cell apoptosis via disruption of glycolysis in ovarian aging
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Xuehan Zhao, Feiyan Zhao, Long Yan, Jiaqi Wu, Ying Fang, Cong Wang, Zhimin Xin, and Xiaokui Yang
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Granulosa cell ,Follicular development ,lncRNA ,Transcriptomics ,SNHG18 ,Ovarian aging ,Gynecology and obstetrics ,RG1-991 - Abstract
Abstract Background In-depth understanding of dynamic expression profiles of human granulosa cells (GCs) during follicular development will contribute to the diagnostic and targeted interventions for female infertility. However, genome-scale analysis of long non-coding ribonucleic acid (lncRNA) in GCs across diverse developmental stages is challenging. Meanwhile, further research is needed to determine how aberrant lncRNA expression participates in ovarian diseases. Methods Granulosa cell-related lncRNAs data spanning five follicular development stages were retrieved and filtered from the NCBI dataset (GSE107746). Stage-specific lncRNA expression patterns and mRNA-lncRNA co-expression networks were identified with bioinformatic approaches. Subsequently, the expression pattern of SNHG18 was detected in GCs during ovarian aging. And SNHG18 siRNA or overexpression plasmids were transfected to SVOG cells in examining the regulatory roles of SNHG18 in GC proliferation and apoptosis. Moreover, whether PKCɛ/SNHG18 signaling take part in GC glycolysis via ENO1 were verified in SVOG cells. Results We demonstrated that GC-related lncRNAs were specifically expressed across different developmental stages, and coordinated crucial biological functions like mitotic cell cycle and metabolic processes in the folliculogenesis. Thereafter, we noticed a strong correlation of PRKCE and SNHG18 expression in our analysis. With downregulated SNHG18 of GCs identified in the context of ovarian aging, SNHG18 knockdown could further induce cell apoptosis, retard cell proliferation and exacerbate DNA damage in SVOG cell. Moreover, downregulated PKCɛ/SNHG18 pathway interrupted the SVOG cell glycolysis by lowering the ENO1 expression. Conclusions Altogether, our results revealed that folliculogenesis-related lncRNA SNHG18 participated in the pathogenesis of ovarian aging, which may provide novel biomarkers for ovarian function and new insights for the infertility treatment.
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- 2024
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10. Role of the lncRNA/Wnt signaling pathway in digestive system cancer: a literature review
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Penghui Li, Xiao Ma, and Di Huang
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LncRNA ,Wnt pathway ,Digestive system tumors ,Diagnosis ,Therapeutic targets ,Medicine - Abstract
Abstract The long noncoding RNA (lncRNA)/Wingless (Wnt) axis is often dysregulated in digestive system tumors impacting critical cellular processes. Abnormal expression of specific Wnt-related lncRNAs such as LINC01606 (promotes motility), SLCO4A1-AS1 (promotes motility), and SH3BP5-AS1 (induces chemoresistance), plays a crucial role in these malignancies. These lncRNAs are promising targets for cancer diagnosis and therapy, offering new treatment perspectives. The lncRNAs, NEF and GASL1, differentially expressed in plasma show diagnostic potential for esophageal squamous cell carcinoma and gastric cancer, respectively. Additionally, Wnt pathway inhibitors like XAV-939 have demonstrated preclinical efficacy, underscoring their therapeutic potential. This review comprehensively analyzes the lncRNA/Wnt axis, highlighting its impact on cell proliferation, motility, and chemoresistance. By elucidating the complex molecular mechanisms of the lncRNA/Wnt axis, we aim to identify potential therapeutic targets for digestive system tumors to pave the way for the development of targeted treatment strategies.
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- 2024
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11. High expression of small nucleolar host gene RNA may predict poor prognosis of Hepatocellular carcinoma, based on systematic reviews and meta-analyses
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Sheng-qi Du, Ya-Tong Liu, Fen Yang, Pei-xue Wang, and Jun Zhang
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lncRNA ,SNHG ,Hepatocellular carcinoma ,Prognosis ,Meta-analysis ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background The prognosis of patients with hepatocellular cancer is substantially correlated with the abnormal expression of growing long non-coding RNA small nucleolar host gene RNA (SNHG) families in liver cancer tissues. This study aimed to examine the relationship between SNHG expression and liver cancer prognosis. Methods After searching six internet databases, pertinent manuscripts were found based on inclusion and exclusion criteria. To determine whether SNHG expression levels affect liver cancer prognosis, raw data were collected and hazard ratios (HRs) and odds ratios (ORs) were calculated. The results were examined for potential publication bias using the sensitivity analysis and Beeg’s test. Results Most SNHG family members were up-regulated in liver cancer tissues. High SNHG expression predicts poor liver cancer outcomes of, including overall survival (OS) (HR: 1.697, 95% confidence interval [CI]: 1.373–2.021), especially SNHG5 (the HR of OS is 4.74, 95%CI range from 1.35 to 6.64), progression-free survival (HR: 1.85, 95% CI: 1.25–2.73), tumor, node, metastasis (TNM) stage (OR: 1.696, 95% CI: 1.436–2.005), lymph node metastasis (OR: 2.383, 95% CI: 1.098–5.173), and tumor size (OR: 1363, 95% CI: 1.165–1.595). The OS results were found to be reliable and robust, as indicated by the sensitivity analysis. Additionally, Beeg’s test demonstrated the absence of any potential publication bias for each result. Conclusion In liver cancer tissues, most SNHGs are highly expressed, which may signal poor prognosis. SNHG has the potential to be an intriguing predictive marker and a prospective therapeutic target for liver cancer.
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- 2024
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12. Identification of key genes and long non‑coding RNA expression profiles in osteoporosis with rheumatoid arthritis based on bioinformatics analysis
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Jin-yu An, Xing-na Ma, Hui-long Wen, and Hui-dong Hu
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Osteoporosis ,Rheumatoid arthritis ,lncRNA ,Differentially expressed genes ,Protein-protein interaction network ,Co-expression network ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background Although rheumatoid arthritis (RA) is a chronic systemic tissue disease often accompanied by osteoporosis (OP), the molecular mechanisms underlying this association remain unclear. This study aimed to elucidate the pathogenesis of RA and OP by identifying differentially expressed mRNAs (DEmRNAs) and long non-coding RNAs (lncRNAs) using a bioinformatics approach. Methods Expression profiles of individuals diagnosed with OP and RA were retrieved from the Gene Expression Omnibus database. Differential expression analysis was conducted. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) pathway enrichment analyses were performed to gain insights into the functional categories and molecular/biochemical pathways associated with DEmRNAs. We identified the intersection of common DEmRNAs and lncRNAs and constructed a protein-protein interaction (PPI) network. Correlation analysis between the common DEmRNAs and lncRNAs facilitated the construction of a coding-non-coding network. Lastly, serum peripheral blood mononuclear cells (PBMCs) from patients with RA and OP, as well as healthy controls, were obtained for TRAP staining and qRT-PCR to validate the findings obtained from the online dataset assessments. Results A total of 28 DEmRNAs and 2 DElncRNAs were identified in individuals with both RA and OP. Chromosomal distribution analysis of the consensus DEmRNAs revealed that chromosome 1 had the highest number of differential expression genes. GO and KEGG analyses indicated that these DEmRNAs were primarily associated with " platelets (PLTs) degranulation”, “platelet alpha granules”, “platelet activation”, “tight junctions” and “leukocyte transendothelial migration”, with many genes functionally related to PLTs. In the PPI network, MT-ATP6 and PTGS1 emerged as potential hub genes, with MT-ATP6 originating from mitochondrial DNA. Co-expression analysis identified two key lncRNA-mRNA pairs: RP11 − 815J21.2 with MT − ATP6 and RP11 − 815J21.2 with PTGS1. Experimental validation confirmed significant differential expression of RP11-815J21.2, MT-ATP6 and PTGS1 between the healthy controls and the RA + OP groups. Notably, knockdown of RP11-815J21.2 attenuated TNF + IL-6-induced osteoclastogenesis. Conclusions This study successfully identified shared dysregulated genes and potential therapeutic targets in individuals with RA and OP, highlighting their molecular similarities. These findings provide new insights into the pathogenesis of RA and OP and suggest potential avenues for further research and targeted therapies.
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- 2024
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13. Immune-related gene signature improves prognosis prediction in patients with breast cancer and associates it with tumor immunity and inflammatory response
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Haiping Zhang, Lu Sun, Jingjing Liu, Jing Wang, Lingchao Meng, Yuan Gao, Jingwu Li, and Qi Zhou
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Immune checkpoint inhibitors ,Immune cells ,lncRNA ,Immune prognostic signature ,Breast cancer ,Gynecology and obstetrics ,RG1-991 ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract Background The prognostic potential of immune-related genes, particularly immune checkpoint inhibitors (ICIs) and long non-coding RNAs (lncRNAs), is gaining attention for evaluating the prognosis of breast cancer patients. Methods We analyzed 23 datasets to identify 15 ICI-related mRNAs and 5 immune-related lncRNAs, creating a robust immune score (IS). This score was used to classify patients into high and low IS groups and assess their survival outcomes. Results Patients with high IS showed significantly poorer overall survival (OS) and progression-free survival (PFS) compared to those with low IS. Multivariate Cox regression analysis confirmed IS as an independent prognostic factor. Additionally, high IS was associated with higher mutation loads and neoantigen profiles, while low IS correlated with enhanced immune cell infiltration. Conclusions The immune score developed from ICI-related mRNAs and lncRNAs effectively predicts the prognosis of breast cancer patients and highlights the differential immune and inflammatory responses between patients with varying levels of immune score. This underscores the relevance of IS in guiding therapeutic decisions and tailoring patient management strategies in clinical settings.
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- 2024
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14. Genetic variants of LncRNAs HOTTIP and MEG3 influence nasopharyngeal carcinoma susceptibility and clinicopathologic characteristics in the Southern Chinese population
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Xiaoxia Lao, Yujie Wang, Rongxin Huang, Yanying He, Huabiao Lu, and Dan Liang
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Nasopharyngeal carcinoma ,lncRNA ,HOTTIP ,MEG3 ,Polymorphism ,Genotypes ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Objective Recent studies have indicated that HOTTIP and MEG3 are associated with the initiation and progression of various types of tumors, including nasopharyngeal carcinoma (NPC). This investigation aimed to elucidate the impact of HOTTIP and MEG3 polymorphisms on the susceptibility and clinicopathologic characteristics of NPC. Methods This research employed next-generation sequencing and multiplex PCR to assess the polymorphisms of HOTTIP rs1859168 and MEG3 rs7158663 in 200 NPC and 200 healthy individuals respectively. HOTTIP and MEG3 expression were assessed via qRT-PCR assessment. Furthermore, the genotypes and alleles frequency of rs1859168 and rs7158663 were compared between healthy and NPC individuals to elucidate their influence on NPC susceptibility and relation with clinicopathologic characteristics. Results In comparison with the healthy cohort, the presence of HOTTIP rs1859168 CC genotype and the C allele were markedly linked with increased NPC incidence (p
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- 2024
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15. GRASLND regulates melanoma cell progression by targeting the miR-218-5p/STAM2 axis
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Aiwei Ma, Wenqi Shi, Liyun Chen, Zijian Huang, Yiwen Zhang, Zixuan Tang, Wenshi Jiang, Mengjing Xu, Jianda Zhou, Wancong Zhang, and Shijie Tang
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SKCM ,lncRNA ,Prognosis ,Immunotherapy ,Biomarker ,Medicine - Abstract
Abstract Background Increasing evidence suggests that long noncoding RNAs (lncRNAs) play important regulatory roles in biological processes and are dysregulated in numerous tumors. The lncRNA GRASLND functions as an oncogene in many cancers, but its role in skin cutaneous melanoma (SKCM) requires further investigation. Methods SiRNA transfection, wound − healing and transwell assays were performed to evaluate the effect of GRASLND on cellular function. Results The present study demonstrated that GRASLND expression is increased in SKCM tissues and cell lines. The high expression of GRASLND was correlated with poor prognosis and immunotherapy outcomes. Knockdown of GRASLND significantly inhibited cell migration and invasion. In addition, we found that miR-218-5p directly binds to its binding site on GRASLND, and GRASLND and miR-218-5p demonstrate mutual inhibition. Furthermore, the miR-218-5p inhibitor partially eliminated the knockdown of GRASLND and inhibited its expression. We also demonstrated that GRASLND acts as a miR-218-5p sponge that positively regulates STAM2 expression in SKCM cells. Conclusion In summary, these data suggest that GRASLND functions by regulating miR-218-5p/STAM2 expression, suggesting an important role for the lncRNA‒miRNA–mRNA functional network and a new potential therapeutic target for SKCM.
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- 2024
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16. Oncogenic LINC00698 suppresses apoptosis of melanoma stem cells to promote tumorigenesis via LINC00698-miR-3132-TCF7/hnRNPM axis
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Anas Mohammed, Ahmad Khan, and Xiaobo Zhang
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Melanoma stem cells ,LncRNA ,Apoptosis ,Stemness ,Tumorigenesis ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Cytology ,QH573-671 - Abstract
Abstract Melanoma progression depends on melanoma stem cells (MSCs), which are distinguished by the distinct dysregulated genes. As the key factors in the dysregulation of genes, long non-coding RNAs (lncRNAs) take great effects on MSCs. However, the underlying mechanism of lncRNAs in MSCs has not been extensively characterized. To address the roles of lncRNAs in MSCs, LINC00698 was characterized in this study. The results revealed that LINC00698 was upregulated in MSCs, showing its important role in MSCs. The further data indicated that the LINC00698 silencing triggered cell cycle arrest in the G0/G1 phase and apoptosis of MSCs. LINC00698 could directly interact with miR-3132 to upregulate the expression of TCF7, which was required for sustaining the stemness and the tumorigenic potency of MSCs. At the same time, LINC00698 could bind to the hnRNPM protein to enhance the protein stability, thus suppressing apoptosis and promoting the stemness of MSCs. Furthermore, the in vivo data demonstrated that LINC00698 was essential for tumorigenesis of MSCs via the LINC00698-miR-3132-TCF7/hnRNPM axis. Therefore, our findings contributed novel insights into the underlying mechanism of melanoma progression.
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- 2024
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17. Astragalus mongholicus bunge and panax notoginseng formula (A&P) improves renal fibrosis in UUO mice via inhibiting the long non-coding RNA A330074K22Rik and downregulating ferroptosis signaling
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Xia Zhong, Yue Huang, Jian Jia, Jian Liu, Hongwei Su, Qiongdan Hu, Ruizhi Tan, and Li Wang
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Renal fibrosis ,Chinese medicine ,Ferroptosis ,LncRNA ,Astragalus mongholicus Bunge and Panax notoginseng formula (A&P) ,Other systems of medicine ,RZ201-999 - Abstract
Abstract Background Chronic kidney disease (CKD) and its associated end-stage renal disease (ESRD) are significant health problems that pose a threat to human well-being. Renal fibrosis is a common feature and ultimate pathological outcome of various CKD leading to ESRD. The Astragalus mongholicus Bunge and Panax notoginseng formula (A&P) is a refined compound formulated by our research group, which has been clinically administered for over a decade and has demonstrated the ability to improve the inflammatory state of various acute or chronic kidney diseases. However, the underlying mechanism by which A&P ameliorates renal fibrosis remains unclear. Methods We established a mouse model by surgically ligating the unilateral ureter to induce renal injury in vivo. And we utilized renal in situ electroporation of a plasmid with low LncRNA A33 expression to establish the unilateral ureteral obstruction(UUO)mouse model. In vitro, we stimulated primary tubular epithelial cells(pTEC) injury using TGF-β1, siRNA-A33, and pcDNA3.1-A33 plasmids were transfected into pTECs to respectively knockdown and overexpress LncRNA A33, and both in vitro and in vivo models were intervened with A&P. Results The results demonstrated that A&P effectively alleviated renal fibrosis in mice. Subsequent findings indicated high expression of LncRNA A33 in the kidneys of UUO mice and TGF-β1-induced renal tubular cells. In situ, renal electroporation of a plasmid with reduced LncRNA A33 expression revealed that inhibiting LncRNA A33 significantly improved renal fibrosis in UUO mice. Moreover, A&P effectively suppressed LncRNA A33 expression both in vitro and in vivo. Subsequent downregulation of LncRNA A33 in renal tubular epithelial cells resulted in the downregulation of numerous fibrotic markers, a significant inhibition of LncRNA A33, and a notable reduction in downstream ferroptosis signaling. Cell experiments demonstrated that A&P improved renal fibrosis in UUO mice by inhibiting LncRNA A33 and downregulating ferroptosis signaling. Conclusion Through the inhibition of LncRNA A33 and subsequent downregulation of ferroptosis signaling, A&P showed potential as a therapeutic approach for improving renal fibrosis in UUO mice, providing a potential treatment avenue for CKD.
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- 2024
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18. Transcriptome analysis suggested that lncRNAs regulate rapeseed seedlings in responding to drought stress by coordinating the phytohormone signal transduction pathways
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Xiaoyu Tan, Weihua Long, Ni Ma, Shifei Sang, and Shanya Cai
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Brassica napus L. ,Water stress ,Rehydration ,lncRNA ,Signal transduction ,Biotechnology ,TP248.13-248.65 ,Genetics ,QH426-470 - Abstract
Abstract The growth, yield, and seed quality of rapeseed are negatively affected by drought stress. Therefore, it is of great value to understand the molecular mechanism behind this phenomenon. In a previous study, long non-coding RNAs (lncRNAs) were found to play a key role in the response of rapeseed seedlings to drought stress. However, many questions remained unanswered. This study was the first to investigate the expression profile of lncRNAs not only under control and drought treatment, but also under the rehydration treatment. A total of 381 differentially expressed lncRNA and 10,253 differentially expressed mRNAs were identified in the comparison between drought stress and control condition. In the transition from drought stress to rehydration, 477 differentially expressed lncRNAs and 12,543 differentially expressed mRNAs were detected. After identifying the differentially expressed (DE) lncRNAs, the comprehensive lncRNAs-engaged network with the co-expressed mRNAs in leaves under control, drought and rehydration was investigated. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of co-expressed mRNAs identified the most significant pathways related with plant hormones (expecially abscisic acid, auxin, cytokinins, and gibberellins) in the signal transduction. The genes, co-expressed with the most-enriched DE-lncRNAs, were considered as the most effective candidates in the water-loss and water-recovery processes, including protein phosphatase 2 C (PP2C), ABRE-binding factors (ABFs), and SMALL AUXIN UP-REGULATED RNAs (SAURs). In summary, these analyses clearly demonstrated that DE-lncRNAs can act as a regulatory hub in plant-water interaction by controlling phytohormone signaling pathways and provided an alternative way to explore the complex mechanisms of drought tolerance in rapeseed.
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- 2024
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19. Current understanding of functional peptides encoded by lncRNA in cancer
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Hua Tian, Lu Tang, Zihan Yang, Yanxi Xiang, Qi Min, Mengshuang Yin, Huili You, Zhangang Xiao, and Jing Shen
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Cancer ,Coding potential ,Functional peptides ,lncRNA ,Small ORF ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Cytology ,QH573-671 - Abstract
Abstract Dysregulated gene expression and imbalance of transcriptional regulation are typical features of cancer. RNA always plays a key role in these processes. Human transcripts contain many RNAs without long open reading frames (ORF, > 100 aa) and that are more than 200 bp in length. They are usually regarded as long non-coding RNA (lncRNA) which play an important role in cancer regulation, including chromatin remodeling, transcriptional regulation, translational regulation and as miRNA sponges. With the advancement of ribosome profiling and sequencing technologies, increasing research evidence revealed that some ORFs in lncRNA can also encode peptides and participate in the regulation of multiple organ tumors, which undoubtedly opens a new chapter in the field of lncRNA and oncology research. In this review, we discuss the biological function of lncRNA in tumors, the current methods to evaluate their coding potential and the role of functional small peptides encoded by lncRNA in cancers. Investigating the small peptides encoded by lncRNA and understanding the regulatory mechanisms of these functional peptides may contribute to a deeper understanding of cancer and the development of new targeted anticancer therapies.
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- 2024
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20. CircRNA and lncRNA-associated competing endogenous RNA networks in medulloblastoma: a scoping review
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Fatemeh Nejadi Orang and Mahdi Abdoli Shadbad
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CeRNA ,CircRNA ,LncRNA ,Medulloblastoma ,MiRNA ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Cytology ,QH573-671 - Abstract
Abstract Background Medulloblastoma is one of the common primary central nervous system (CNS) malignancies in pediatric patients. The main treatment is surgical resection preceded and/or followed by chemoradiotherapy. However, their serious side effects necessitate a better understanding of medulloblastoma biology to develop novel therapeutic options. Main body Circular RNA (circRNA) and long non-coding RNA (lncRNA) regulate gene expression via microRNA (miRNA) pathways. Although growing evidence has highlighted the significance of circRNA and lncRNA-associated competing endogenous RNA (ceRNA) networks in cancers, no study has comprehensively investigated them in medulloblastoma. For this aim, the Web of Science, PubMed, Scopus, and Embase were systematically searched to obtain the relevant papers published before 16 September 2023, adhering to the PRISMA-ScR statement. HOTAIR, NEAT1, linc-NeD125, HHIP-AS1, CRNDE, and TP73-AS1 are the oncogenic lncRNAs, and Nkx2-2as is a tumor-suppressive lncRNA that develop lncRNA-associated ceRNA networks in medulloblastoma. CircSKA3 and circRNA_103128 are upregulated oncogenic circRNAs that develop circRNA-associated ceRNA networks in medulloblastoma. Conclusion In summary, this study has provided an overview of the existing evidence on circRNA and lncRNA-associated ceRNA networks and their impact on miRNA and mRNA expression involved in various signaling pathways of medulloblastoma. Suppressing the oncogenic ceRNA networks and augmenting tumor-suppressive ceRNA networks can provide ample opportunities for medulloblastoma treatment.
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- 2024
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21. Identification and functional analysis of long non-coding RNA (lncRNA) and metabolites response to mowing in hulless barley (Hordeum vulgare L. var. nudum hook. f.)
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Yixiong Bai, Jiaqi He, Youhua Yao, Likun An, Yongmei Cui, Xin Li, Xiaohua Yao, Shanshan Xiao, and Kunlun Wu
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Hulless barley ,lncRNA ,Metabolome ,Mowing ,Plant hormones ,Cytokinin ,Botany ,QK1-989 - Abstract
Abstract Background Hulless barley (Hordeum vulgare L. var. nudum Hook. f.) is a significant cereal crop and a substantial source of forage for livestock. Long non-coding RNAs (lncRNAs) and metabolites play crucial roles in the nutrient accumulation and regeneration of hulless barley plants following mowing. The study aimed to identify differentially expressed lncRNAs and metabolites in hulless barley plants by analyzing transcriptomic and metabolomic datasets at 2 h, 24 h, and 72 h following mowing. Results The study revealed that 190, 90, and 438 lncRNA genes were differentially expressed at the 2 h, 24 h, and 72 h time points compared to the non-mowing control. We identified 14 lncRNA genes—11 downregulated and 3 upregulated—showing consistently significant differential expression across all time points after mowing. These differentially expressed lncRNAs target genes involved in critical processes such as cytokinin signaling, cell wall degradation, storage protein accumulation, and biomass increase. In addition, we identified ten differentially expressed metabolites targeting diverse metabolic pathways, including plant hormones, alkaloids, and flavonoids, before and after mowing at various time points. Endogenous hormone analysis revealed that cytokinin most likely played a crucial role in the regeneration of hulless barley after mowing. Conclusions This study created a comprehensive dataset of lncRNAs, metabolites, and hormones in hulless barley after mowing, revealing valuable insights into the functional characteristics of lncRNAs, metabolites, and hormones in regulating plant regeneration. The results indicated that cytokinin plays a significant role in facilitating the regeneration process of hulless barley after mowing. This comprehensive dataset is an invaluable resource for better understanding the complex mechanisms that underlie plant regeneration, with significant implications for crop improvement.
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- 2024
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22. Visfatin (NAMPT) affects global gene expression in porcine anterior pituitary cells during the mid-luteal phase of the oestrous cycle
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Kamil Dobrzyn, Grzegorz Kopij, Marta Kiezun, Ewa Zaobidna, Marlena Gudelska, Barbara Zarzecka, Lukasz Paukszto, Agnieszka Rak, Nina Smolinska, and Tadeusz Kaminski
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Alternative splicing ,Anterior pituitary ,Differentially expressed genes ,lncRNA ,Oestrous cycle ,Pig ,Animal culture ,SF1-1100 ,Veterinary medicine ,SF600-1100 - Abstract
Abstract Background The pituitary belongs to the most important endocrine glands involved in regulating reproductive functions. The proper functioning of this gland ensures the undisturbed course of the oestrous cycle and affects the female’s reproductive potential. It is believed that visfatin, a hormone belonging to the adipokine family, may regulate reproductive functions in response to the female’s metabolic state. Herein we verified the hypothesis that suggests a modulatory effect of visfatin on the anterior pituitary transcriptome during the mid-luteal phase of the oestrous cycle. Results RNA-seq analysis of the porcine anterior pituitary cells revealed changes in the expression of 202 genes (95 up-regulated and 107 down-regulated in the presence of visfatin, when compared to the non-treated controls), assigned to 318 gene ontology terms. We revealed changes in the frequency of alternative splicing events (235 cases), as well as long noncoding RNA expression (79 cases) in the presence of the adipokine. The identified genes were associated, among others, with reproductive system development, epithelial cell proliferation, positive regulation of cell development, gland morphogenesis and cell chemotaxis. Conclusions The obtained results indicate a modulatory influence of visfatin on the regulation of the porcine transcriptome and, in consequence, pituitary physiology during the mid-luteal phase of the oestrous cycle.
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- 2024
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23. Positive feedback loop of c-myc/XTP6/NDH2/NF-κB to promote malignant progression in glioblastoma
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Feng Xiao, Hong Zhu, Yaping Xiong, Yun Guo, Zhe Zhang, Jie Zeng, Yao Xiao, Bin Liao, Xuesong Shang, Siyi Zhao, Guowen Hu, Kai Huang, and Hua Guo
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Positive feedback loop ,Glioblastoma ,LncRNA ,XTP6 ,NF-κB signaling pathway ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Recent studies have highlighted the significant role of the NF-κB signaling pathway in the initiation and progression of cancer. Furthermore, long noncoding RNAs (lncRNAs) have been identified as pivotal regulators in sustaining the NF-κB signaling pathway’s functionality. Despite these findings, the underlying molecular mechanisms through which lncRNAs influence the NF-κB pathway remain largely unexplored. Methods Bioinformatic analyses were utilized to investigate the differential expression and prognostic significance of XTP6. The functional roles of XTP6 were further elucidated through both in vitro and in vivo experimental approaches. To estimate the interaction between XTP6 and NDH2, RNA pulldown and RNA Immunoprecipitation (RIP) assays were conducted. The connection between XTP6 and the IκBα promoter was examined using Chromatin Isolation by RNA Purification (ChIRP) assays. Additionally, Chromatin Immunoprecipitation (ChIP) assays were implemented to analyze the binding affinity of c-myc to the XTP6 promoter, providing insights into the regulatory mechanisms at play. Results XTP6 was remarkedly upregulated in glioblastoma multiforme (GBM) tissues and was connected with adverse prognosis in GBM patients. Our investigations revealed that XTP6 can facilitate the malignant progression of GBM both in vitro and in vivo. Additionally, XTP6 downregulated IκBα expression by recruiting NDH2 to the IκBα promoter, which resulted in elevated levels of H3K27me3, thereby reducing the transcriptional activity of IκBα. Moreover, the progression of GBM was further driven by the c-myc-mediated upregulation of XTP6, establishing a positive feedback loop with IκBα that perpetuated the activation of the NF-κB signaling pathway. Notably, the application of an inhibitor targeting the NF-κB signaling pathway effectively inhibited the continuous activation induced by XTP6, leading to a significant reduction in tumor formation in vivo. Conclusion The results reveal that XTP6 unveils an innovative epigenetic mechanism instrumental in the sustained activation of the NF-κB signaling pathway, suggesting a promising therapeutic target for the treatment of GBM.
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- 2024
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24. Identification and analysis of short-term and long-term salt-associated lncRNAs in the leaf of Avicennia marina
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Lingling Wang, Yixuan Fu, Zixin Yuan, Jingyi Wang, and Yali Guan
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LncRNA ,Avicennia marina ,Mangrove ,Salt stress ,Leaf specificity ,Botany ,QK1-989 - Abstract
Abstract As a highly salt-resistant mangrove, Avicennia marina can thrive in the hypersaline water. The leaves of Avicennia marina play a crucial role in salinity stress adaptability by secreting salt. Although the functions of long non-coding RNAs (lncRNAs) in leaves remain unknown, they have emerged as regulators in leaf development, aging and salt response. In this study, we employed transcriptomic data of both short-term and long-term salt treated leaves to identify salt-associated lncRNAs of leaf tissue. As a result, 687 short-term and 797 long-term salt-associated lncRNAs were identified. Notably, both short-term and long-term salt-associated lncRNAs exhibited slightly longer lengths and larger exons, but smaller introns compared with salt-non-associated lncRNAs. Furthermore, salt-associated lncRNAs also displayed higher tissue-specificity than salt-non-associated lncRNAs. Most of the salt-associated lncRNAs were common to short- and long-term salt treatments. And about one fifth of the downregulated salt-associated lncRNAs identified both in two terms were leaf tissue-specific lncRNAs. Besides, these leaf-specific lncRNAs were found to be involved in the oxidation–reduction and photosynthesis processes, as well as several metabolic processes, suggesting the noticeable functions of salt-associated lncRNAs in regulating salt responses of Avicennia marina leaves.
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- 2024
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25. FOXD2-AS1 promotes malignant cell behavior in oral squamous cell carcinoma via the miR-378 g/CRABP2 axis
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Shaoyong Guo, Bixia Huang, Zhisong You, Zhenzhi Luo, Da Xu, Jieru Zhang, and Jialin Lin
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ceRNA network ,Functional experiments ,Invasion ,lncRNA ,Migration ,Dentistry ,RK1-715 - Abstract
Abstract Background Oral squamous cell cancer (OSCC) is a prevalent malignancy in oral cavity, accounting for nearly 90% of oral malignancies. It ranks sixth among the most common types of cancer worldwide and is responsible for approximately 145,000 deaths each year. It is widely accepted that noncoding RNAs participate cancer development in competitive regulatory interaction, knowing as competing endogenous RNA (ceRNA) network, whereby long non-coding RNA (lncRNA) function as decoys of microRNAs to regulate gene expression. LncRNA FOXD2-AS1 was reported to exert an oncogenic role in OSCC. Nevertheless, the ceRNA network mediated by FOXD2-AS1 was not investigated yet. This study aimed to explore the effect of FOXD2-AS1 on OSCC cell process and the underlying ceRNA mechanism. Methods FOXD2-AS1 expression in OSCC cells were determined via reverse transcription and quantitative polymerase chain reaction. Short hairpin RNA targeting FOXD2-AS1 was transfected into OSCC cells to silence FOXD2-AS1 expression. Then, loss-of-function experiments (n = 3 each assay) were performed to measure cell proliferation, apoptosis, migration, and invasion using colony formation, TdT-mediated dUTP Nick-End Labeling, wound healing and Transwell assays, respectively. RNA binding relation was verified by RNA immunoprecipitation and luciferase reporter assays. Rescue experiments were designed to validate whether FOXD2-AS1 affects cell behavior via the gene cellular retinoic acid binding protein 2 (CRABP2). Statistics were processed by GraphPad Prism 6.0 Software and SPSS software. Results FOXD2-AS1 was significantly upregulated in Cal27 and SCC9 cells (6.8 and 6.4 folds). In response to FOXD2-AS1 knockout, OSCC cell proliferation, migration and invasion were suppressed (approximately 50% decrease) while OSCC cell apoptosis was enhanced (more than two-fold increase). FOXD2-AS1 interacted with miR-378 g to alter CRABP2 expression. CRABP2 upregulation partly rescued (*p
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- 2024
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26. Regulatory roles of long non-coding RNAs in short-term heat stress in adult worker bees
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Bing Zhang, Chaoying Zhang, Jiangchao Zhang, Surong Lu, Huiting Zhao, Yusuo Jiang, and Weihua Ma
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Apis mellifera ,Cis-regulation ,Heat stress ,lncRNA ,MSTRG.9645.5 ,Network regulation ,Biotechnology ,TP248.13-248.65 ,Genetics ,QH426-470 - Abstract
Abstract Long non-coding RNAs (lncRNAs) are crucial modulators of post-transcriptional gene expression regulation, cell fate determination, and disease development. However, lncRNA functions during short-term heat stress in adult worker bees are poorly understood. Here, we performed deep sequencing and bioinformatic analyses of honeybee lncRNAs. RNA interference was performed by using siRNA targeting the most highly expressed lncRNA. The silencing effect on lncRNA and the relative expression levels of seven heat shock protein (HSP) genes, were subsequently examined. Overall, 7,842 lncRNAs and 115 differentially expressed lncRNAs (DELs) were identified in adult worker bees following heat stress exposure. Structural analysis revealed that the overall expression abundance, length of transcripts, exon number, and open reading frames of lncRNAs were lower than those of mRNAs. GO analysis revealed that the target genes were mainly involved in “metabolism,” “protein folding,” “response to stress,” and “signal transduction” pathways. KEGG analysis indicated that the “protein processing in endoplasmic reticulum” and “longevity regulating pathway-multiple species” pathways were most enriched. Quantitative real-time polymerase chain reaction (qRT-PCR) detection of the selected DELs confirmed the reliability of the sequencing data. Moreover, the siRNA experiment indicated that feeding siRNA yielded a silencing efficiency of 77.51% for lncRNA MSTRG.9645.5. Upon silencing this lncRNA, the expression levels of three HSP genes were significantly downregulated (p
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- 2024
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27. CRISPR-Cas13d screens identify KILR, a breast cancer risk-associated lncRNA that regulates DNA replication and repair
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Lu Wang, Mainá Bitar, Xue Lu, Sebastien Jacquelin, Sneha Nair, Haran Sivakumaran, Kristine M. Hillman, Susanne Kaufmann, Rebekah Ziegman, Francesco Casciello, Harsha Gowda, Joseph Rosenbluh, Stacey L. Edwards, and Juliet D. French
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Breast cancer ,GWAS ,Long noncoding RNA ,lncRNA ,Genetic variants ,CRISPR ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Long noncoding RNAs (lncRNAs) have surpassed the number of protein-coding genes, yet the majority have no known function. We previously discovered 844 lncRNAs that were genetically linked to breast cancer through genome-wide association studies (GWAS). Here, we show that a subset of these lncRNAs alter breast cancer risk by modulating cell proliferation, and provide evidence that a reduced expression on one lncRNA increases breast cancer risk through aberrant DNA replication and repair. Methods We performed pooled CRISPR-Cas13d-based knockdown screens in breast cells to identify which of the 844 breast cancer-associated lncRNAs alter cell proliferation. We selected one of the lncRNAs that increased cell proliferation, KILR, for follow-up functional studies. KILR pull-down followed by mass spectrometry was used to identify binding proteins. Knockdown and overexpression studies were performed to assess the mechanism by which KILR regulates proliferation. Results We show that KILR functions as a tumor suppressor, safeguarding breast cells against uncontrolled proliferation. The half-life of KILR is significantly reduced by the risk haplotype, revealing an alternative mechanism by which variants alter cancer risk. Mechanistically, KILR sequesters RPA1, a subunit of the RPA complex required for DNA replication and repair. Reduced KILR expression promotes breast cancer cell proliferation by increasing the available pool of RPA1 and speed of DNA replication. Conversely, KILR overexpression promotes apoptosis in breast cancer cells, but not normal breast cells. Conclusions Our results confirm lncRNAs as mediators of breast cancer risk, emphasize the need to annotate noncoding transcripts in relevant cell types when investigating GWAS variants and provide a scalable platform for mapping phenotypes associated with lncRNAs.
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- 2024
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28. Ethanol responsive lnc171 promotes migration and invasion of HCC cells via mir-873-5p/ZEB1 axis
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Shiping Huang, Zhouxiang Liao, Xiao He, Zhenyu Song, Xi Fang, Sha Wen, Lichao Yang, Hui Li, Qi Zhang, Wanling Mo, Xiaojing Cheng, Min He, and Xuejing Huang
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Hepatocellular carcinoma ,lncRNA ,ceRNA ,Ethanol ,Migration ,Invasion ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Backgrounds Long nonconding RNAs (lncRNAs) have been found to be a vital regulatory factor in the development process of human cancer, and could regarded as diagnostic or prognostic biomarkers for human cancers. Here, we aim to confirm the expression and molecular mechanism of RP11-171K16.5 (lnc171) in hepatocellular carcinoma (HCC). Methods Screening of differentially expressed lncRNAs by RNA sequencing. Expression level of gene was studied by quantitative real-time PCR (qRT-PCR). The effects of lnc171, mir-873-5p, and ethanol on migration and invasion activity of cells were studied used transwell assay, and luciferase reporter assay was used to confirm the binding site. Results RNA sequencing showed that lnc171 was markedly up-regulated in HCC. siRNA-mediated knockdown of lnc171 repressed the migration and invasion ability of HCC cells. Bioinformatic analysis, dual luciferase reporter assay, and qRT-PCR indicated that lnc171 interacted with mir-873-5p in HCC cells, and Zin-finger E-box binding homeobox (ZEB1) was a downstream target gene of mir-873-5p. In addition, lnc171 could enhance migration and invasion ability of HCC cells by up-regulating ZEB1 via sponging mir-873-5p. More interestingly, ethanol stimulation could up-regulate the increase of lnc171, thereby regulating the expression of competing endogenous RNA (ceRNA) network factors which lnc171 participated in HCC cells. Conclusions Our date demonstrates that lnc171 was a responsive factor of ethanol, and plays a vital role in development of HCC via binding of mir-873-5p.
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- 2024
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29. Predictive significance of glycolysis-associated lncRNA profiles in colorectal cancer progression
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Rui Mao, Chenxin Xu, Quanzheng Zhang, Zheng Wang, Yanjun Liu, Yurui Peng, and Ming Li
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Warburg effect ,Colorectal cancer ,lncRNA ,Prognostic signature ,Nomogram ,Internal medicine ,RC31-1245 ,Genetics ,QH426-470 - Abstract
Abstract Background The Warburg effect is a hallmark characteristic of colorectal cancer (CRC). Despite extensive research, the role of long non-coding RNAs (lncRNAs) in influencing the Warburg effect remains incompletely understood. Our study aims to identify lncRNAs that may modulate the Warburg effect by functioning as competing endogenous RNAs (ceRNAs). Methods Utilizing bioinformatics approaches, we extracted glycolysis-associated gene data from the Kyoto Encyclopedia of Genes and Genomes (KEGG) and identified 101 glycolysis-related lncRNAs in CRC. We employed Univariable Cox regression, Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis, and Multivariable Cox regression to develop a prognostic model comprising four glycolysis-linked lncRNAs. We then constructed a prognostic nomogram integrating this lncRNA model with other relevant clinical parameters. Results The prognostic efficacy of our four-lncRNA signature and its associated nomogram was validated in both training and validation cohorts. Functional assays demonstrated significant glycolysis and hexokinase II (HK2) inhibition following the silencing of RUNDC3A − AS1, a key lncRNA in our prognostic signature, highlighting its regulatory importance in the Warburg effect. Conclusions Our research illuminates the critical role of glycolysis-centric lncRNAs in CRC. The developed prognostic model and nomogram underscore the pivotal prognostic and regulatory significance of the lncRNA RUNDC3A − AS1 in the Warburg effect in colorectal cancer.
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- 2024
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30. Establishment of a placental lncRNA-mRNA expression network for early-onset preeclampsia
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Ya Chen, Ying Zhang, Siyu Xie, Xiangdong Zhou, Lina Zhu, and Yunxia Cao
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LncRNA ,mRNA gene regulatory networks ,Early-onset preeclampsia ,Gynecology and obstetrics ,RG1-991 - Abstract
Abstract Background This study aimed to establish a placental long non-coding RNA (lncRNA)-mRNA expression network for early-onset preeclampsia (early-onset PE). Methods The RNA sequencing data of the GSE14821 dataset were acquired. Several crucial lncRNAs and mRNAs were exerted based on the differential expression analysis of lncRNA and mRNA. By analyzing the differentially expressed lncRNA and mRNA, we constructed a regulatory network to explore the mechanism of the lncRNA in early onset preeclampsia. Results A total of 4436 differentially expressed lncRNAs (DElncRNAs) were identified in early-onset PE placenta samples compared with control placenta samples. Pearson correlation analysis revealed significant correlations between 3659 DElncRNAs and 372 DEmRNAs. KEGG analysis showed that the DEmRNAs were enriched in cytokine-cytokine receptor and hypoxia-inducible factor (HIF)-1 pathways. Several well-known early-onset PE-related mRNAs, such as vascular endothelial growth factor A (VEGFA) and VEGF receptor 1 (FLT1), were involved in the two pathways. Weighted gene co-expression network analysis and cis-regulatory analysis further suggested the involvement of the two pathways and potential DElncRNA-DEmRNA interactions in early-onset PE. Moreover, the upregulation of representative DElncRNAs, such as RP11-211G3.3 and RP11-65J21.3, and DEmRNAs, such as VEGFA and FLT1, were validated in clinical placenta samples from patients with early-onset PE by quantitative reverse transcription PCR. Importantly, overexpression of RP11-65J21.3 significantly promoted the proliferation of HTR-8 trophoblast cells at 72 h after transfection. Conclusions In conclusion, we identified placental DElncRNAs of early-onset PE and established a DElncRNA-DEmRNA network that was closely related to the cytokine-cytokine receptor and HIF-1 pathways. Our results provide potential diagnostic markers and therapeutic targets for early-onset PE management.
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- 2024
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31. Long non-coding RNA SOX2OT in tamoxifen-resistant breast cancer
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Jeeyeon Lee, Eun-Ae Kim, Jieun Kang, Yee Soo Chae, Ho Yong Park, Byeongju Kang, Soo Jung Lee, In Hee Lee, Ji-Young Park, Nora Jee-young Park, and Jin Hyang Jung
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Breast cancer ,Tamoxifen ,Resistance ,LncRNA ,SOX2OT ,Cytology ,QH573-671 - Abstract
Abstract Hormone receptor (HR)-positive breast cancer can become aggressive after developing hormone-treatment resistance. This study elucidated the role of long non-coding RNA (lncRNA) SOX2OT in tamoxifen-resistant (TAMR) breast cancer and its potential interplay with the tumor microenvironment (TME). TAMR breast cancer cell lines TAMR-V and TAMR-H were compared with the luminal type A cell line (MCF-7). LncRNA expression was assessed via next-generation sequencing, RNA extraction, lncRNA profiling, and quantitative RT-qPCR. SOX2OT overexpression effects on cell proliferation, migration, and invasion were evaluated using various assays. SOX2OT was consistently downregulated in TAMR cell lines and TAMR breast cancer tissue. Overexpression of SOX2OT in TAMR cells increased cell proliferation and cell invasion. However, SOX2OT overexpression did not significantly alter SOX2 levels, suggesting an independent interaction within TAMR cells. Kaplan–Meier plot analysis revealed an inverse relationship between SOX2OT expression and prognosis in luminal A and B breast cancers. Our findings highlight the potential role of SOX2OT in TAMR breast cancer progression. The downregulation of SOX2OT in TAMR breast cancer indicates its involvement in resistance mechanisms. Further studies should explore the intricate interactions between SOX2OT, SOX2, and TME in breast cancer subtypes.
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- 2024
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32. Transcriptome analysis reveals the potential lncRNA-mRNA modules involved in genetic male sterility and fertility of Chinese cabbage (brassica rapa L. ssp. pekinensis)
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Xiaochun Wei, Xiaoqing Wang, Yanyan Zhao, Weiwei Chen, Ujjal Kumar Nath, Shuangjuan Yang, Henan Su, Zhiyong Wang, Wenjing Zhang, Baoming Tian, Fang Wei, Yuxiang Yuan, and Xiaowei Zhang
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Chinese cabbage ,Genic male sterility ,GO analysis ,LncRNA ,Botany ,QK1-989 - Abstract
Abstract Background Long non-coding RNAs (lncRNAs) play a crucial role in regulating gene expression vital for the growth and development of plants. Despite this, the role of lncRNAs in Chinese cabbage (Brassica rapa L. ssp. pekinensis) pollen development and male fertility remains poorly understood. Results In this study, we characterized a recessive genic male sterile mutant (366–2 S), where the delayed degradation of tapetum and the failure of tetrad separation primarily led to the inability to form single microspores, resulting in male sterility. To analyze the role of lncRNAs in pollen development, we conducted a comparative lncRNA sequencing using anthers from the male sterile mutant line (366–2 S) and the wild-type male fertile line (366–2 F). We identified 385 differentially expressed lncRNAs between the 366–2 F and 366–2 S lines, with 172 of them potentially associated with target genes. To further understand the alterations in mRNA expression and explore potential lncRNA-target genes (mRNAs), we performed comparative mRNA transcriptome analysis in the anthers of 366–2 S and 366–2 F at two stages. We identified 1,176 differentially expressed mRNAs. Remarkably, GO analysis revealed significant enrichment in five GO terms, most notably involving mRNAs annotated as pectinesterase and polygalacturonase, which play roles in cell wall degradation. The considerable downregulation of these genes might contribute to the delayed degradation of tapetum in 366–2 S. Furthermore, we identified 15 lncRNA-mRNA modules through Venn diagram analysis. Among them, MSTRG.9997-BraA04g004630.3 C (β-1,3-glucanase) is associated with callose degradation and tetrad separation. Additionally, MSTRG.5212-BraA02g040020.3 C (pectinesterase) and MSTRG.13,532-BraA05g030320.3 C (pectinesterase) are associated with cell wall degradation of the tapetum, indicating that these three candidate lncRNA-mRNA modules potentially regulate pollen development. Conclusion This study lays the foundation for understanding the roles of lncRNAs in pollen development and for elucidating their molecular mechanisms in regulating male sterility in Chinese cabbage.
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- 2024
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33. Analyses of lncRNA and mRNA profiles in recurrent atrial fibrillation after catheter ablation
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Huaiguang Tang, Kongmiao Lu, Yan Wang, Yue Shi, Wansheng Ma, Xiaomeng Chen, Bingong Li, and Yibing Shao
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Recurrent atrial fibrillation ,lncRNA ,mRNA ,RNA sequencing ,lncRNA‒mRNA regulatory network ,Medicine - Abstract
Abstract Background Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide. Catheter ablation has become a crucial treatment for AF. However, there is a possibility of atrial fibrillation recurrence after catheter ablation. Our study sought to elucidate the role of lncRNA‒mRNA regulatory networks in late AF recurrence after catheter ablation. Methods We conducted RNA sequencing to profile the transcriptomes of 5 samples from the presence of recurrence after AF ablation (P-RAF) and 5 samples from the absence of recurrence after AF ablation (A-RAF). Differentially expressed genes (DEGs) and long noncoding RNAs (DE-lncRNAs) were analyzed using the DESeq2 R package. The functional correlations of the DEGs were assessed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A protein‒protein interaction (PPI) network was constructed using STRING and Cytoscape. We also established a lncRNA‒mRNA regulatory network between DE-lncRNAs and DEGs using BEDTools v2.1.2 software and the Pearson correlation coefficient method. To validate the high-throughput sequencing results of the hub genes, we conducted quantitative real-time polymerase chain reaction (qRT‒PCR) experiments. Results A total of 28,528 mRNAs and 42,333 lncRNAs were detected. A total of 96 DEGs and 203 DE-lncRNAs were identified between the two groups. GO analysis revealed that the DEGs were enriched in the biological processes (BPs) of “regulation of immune response” and “regulation of immune system process”, the cellular components (CCs) of “extracellular matrix” and “cell‒cell junction”, and the molecular functions (MFs) of “signaling adaptor activity” and “protein–macromolecule adaptor activity”. According to the KEGG analysis, the DEGs were associated with the “PI3K–Akt signaling pathway” and “MAPK signaling pathway.” Nine hub genes (MMP9, IGF2, FGFR1, HSPG2, GZMB, PEG10, GNLY, COL6A1, and KCNE3) were identified through the PPI network. lncRNA-TMEM51-AS1-201 was identified as a core regulator in the lncRNA‒mRNA regulatory network, suggesting its potential impact on the recurrence of AF after catheter ablation through the regulation of COL6A1, FGFR1, HSPG2, and IGF2. Conclusions The recurrence of atrial fibrillation after catheter ablation may be associated with immune responses and fibrosis, with the extracellular matrix playing a crucial role. TMEM51-AS1-201 has been identified as a potential key target for AF recurrence after catheter ablation.
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- 2024
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34. Ferroptosis-related lncRNA NRAV affects the prognosis of hepatocellular carcinoma via the miR-375-3P/SLC7A11 axis
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Ke Zong, Caifeng Lin, Kai Luo, Yilei Deng, Hongfei Wang, Jianfei Hu, Shi Chen, and Renfeng Li
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lncRNA ,Ferroptosis ,Predictive models ,NRAV ,miR-375-3P/SLC7A11 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Ferroptosis has important value in cancer treatment. It is significant to explore the new ferroptosis-related lncRNAs prediction model in Hepatocellular carcinoma (HCC) and the potential molecular mechanism of ferroptosis-related lncRNAs. We constructed a prognostic multi-lncRNA signature based on ferroptosis-related differentially expressed lncRNAs in HCC. qRT-PCR was applied to determine the expression of lncRNA in HCC cells. The biological roles of NRAV in vitro and in vivo were determined by performing a series of functional experiments. Furthermore, dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to confirm the interaction of NRAV with miR-375-3P. We identified 6 differently expressed lncRNAs associated with the prognosis of HCC. Kaplan–Meier analyses revealed the high-risk lncRNAs signature associated with poor prognosis of HCC. Moreover, the AUC of the lncRNAs signature showed utility in predicting HCC prognosis. Further functional experiments show that the high expression of NRAV can strengthen the viciousness of HCC. Interestingly, we found that NRAV can enhance iron export and ferroptosis resistance. Further study showed that NRAV competitively binds to miR-375-3P and attenuates the inhibitory effect of miR-375-3P on SLC7A11, affecting the prognosis of patients with HCC. In conclusion, We developed a novel ferroptosis-related lncRNAs prognostic model with important predictive value for the prognosis of HCC. NRAV is important in ferroptosis induction through the miR-375-3P/SLC7A11 axis.
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- 2024
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35. Long noncoding RNAs and mRNAs profiling in ovary during laying and broodiness in Taihe Black-Bone Silky Fowls (Gallus gallus Domesticus Brisson)
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Yuting Tan, Yunyan Huang, Chunhui Xu, Xuan Huang, Shibao Li, and Zhaozheng Yin
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Broodiness ,Egg production ,lncRNA ,Transcriptomes ,Ovarian follicle development ,Biotechnology ,TP248.13-248.65 ,Genetics ,QH426-470 - Abstract
Abstract Background Broodiness significantly impacts poultry egg production, particularly notable in specific breeds such as the black-boned Silky, characterized by pronounced broodiness. An understanding of the alterations in ovarian signaling is essential for elucidating the mechanisms that influence broodiness. However, comparative research on the characteristics of long non-coding RNAs (lncRNAs) in the ovaries of broody chickens (BC) and high egg-laying chickens (GC) remains scant. In this investigation, we employed RNA sequencing to assess the ovarian transcriptomes, which include both lncRNAs and mRNAs, in eight Taihe Black-Bone Silky Fowls (TBsf), categorized into broody and high egg-laying groups. This study aims to provide a clearer understanding of the genetic underpinnings associated with broodiness and egg production. Results We have identified a total of 16,444 mRNAs and 18,756 lncRNAs, of which 349 mRNAs and 651 lncRNAs exhibited significantly different expression (DE) between the BC and GC groups. Furthermore, we have identified the cis-regulated and trans-regulated target genes of differentially abundant lncRNA transcripts and have constructed an lncRNA-mRNA trans-regulated interaction network linked to ovarian follicle development. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation analyses have revealed that DE mRNAs and the target genes of DE lncRNAs are associated with pathways including neuroactive ligand-receptor interaction, CCR6 chemokine receptor binding, G-protein coupled receptor binding, cytokine-cytokine receptor interaction, and ECM-receptor interaction. Conclusion Our research presents a comprehensive compilation of lncRNAs and mRNAs linked to ovarian development. Additionally, it establishes a predictive interaction network involving differentially abundant lncRNAs and differentially expressed genes (DEGs) within TBsf. This significantly contributes to our understanding of the intricate interactions between lncRNAs and genes governing brooding behavior.
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- 2024
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36. Methylated lncRNAs suppress apoptosis of gastric cancer stem cells via the lncRNA–miRNA/protein axis
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Yuan Ci, Yuan Zhang, and Xiaobo Zhang
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Gastric cancer stem cells ,LncRNA ,Methylation ,Apoptosis ,Stemness ,Cytology ,QH573-671 - Abstract
Abstract Background Long noncoding RNAs (lncRNAs) play essential roles in the tumorigenesis of gastric cancer. However, the influence of lncRNA methylation on gastric cancer stem cells (GCSCs) remains unclear. Methods The N6-methyladenosine (m6A) levels of lncRNAs in gastric cancer stem cells were detected by methylated RNA immunoprecipitation sequencing (MeRIP-seq), and the results were validated by MeRIP-quantitative polymerase chain reaction (qPCR). Specific sites of m6A modification on lncRNAs were detected by single-base elongation- and ligation-based qPCR amplification (SELECT). By constructing and transfecting the plasmid expressing methyltransferase-like 3 (METTL3) fused with catalytically inactivated Cas13 (dCas13b) and guide RNA targeting specific methylation sites of lncRNAs, we obtained gastric cancer stem cells with site-specific methylation of lncRNAs. Reverse transcription (RT)-qPCR and Western blot were used for detecting the stemness of treated gastric cancer stem cells. Results The site-specific methylation of PSMA3-AS1 and MIR22HG suppressed apoptosis and promoted stemness of GCSCs. LncRNA methylation enhanced the stability of PSMA3-AS1 and MIR22HG to suppress apoptosis of GCSCs via the PSMA3-AS1–miR-411-3p– or MIR22HG–miR-24-3p–SERTAD1 axis. Simultaneously, the methylated lncRNAs promoted the interaction between PSMA3-AS1 and the EEF1A1 protein or MIR22HG and the LRPPRC protein, stabilizing the proteins and leading to the suppression of apoptosis. The in vivo data revealed that the methylated PSMA3-AS1 and MIR22HG triggered tumorigenesis of GCSCs. Conclusions Our study revealed the requirement for site-specific methylation of lncRNAs in the tumorigenesis of GCSCs, contributing novel insights into cancer development.
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- 2024
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37. Profiling of long non-coding RNAs in hippocampal–entorhinal system subfields: impact of RN7SL1 on neuroimmune response modulation in Alzheimer’s disease
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Hanyou Liu, Jingying Li, Xue Wang, Shiqi Luo, Dan Luo, Wei Ge, and Chao Ma
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Alzheimer’s disease ,LncRNA ,RN7SL1 ,Neuroimmune processes ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Alzheimer’s disease (AD) is recognized as the predominant cause of dementia, and neuroimmune processes play a pivotal role in its pathological progression. The involvement of long non-coding RNAs (lncRNAs) in AD has attracted widespread attention. Herein, transcriptomic analysis of 262 unique samples extracted from five hippocampal–entorhinal system subfields of individuals with AD pathology and without AD pathology revealed distinctive lncRNA expression profiles. Through differential expression and coexpression analyses, we identified 16 pivotal lncRNAs. Notably, RN7SL1 knockdown significantly modulated microglial responses upon oligomeric amyloid-β stimulation, resulting in a considerable decrease in proinflammatory cytokine production and subsequent neuronal damage. These findings highlight RN7SL1 as an essential neuroimmune-related lncRNA that could serve as a prospective target for AD diagnosis and treatment.
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- 2024
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38. Role of ferroptosis and ferroptosis-related long non'coding RNA in breast cancer
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Shasha Xiang, Wen Yan, Xing Ren, Jianbo Feng, and Xuyu Zu
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LncRNA ,Breast cancer ,Ferroptosis ,Ferroptosis-related lncRNA ,Biomarker ,Cytology ,QH573-671 - Abstract
Abstract Ferroptosis, a therapeutic strategy for tumours, is a regulated cell death characterised by the increased accumulation of iron-dependent lipid peroxides (LPO). Tumour-associated long non-coding RNAs (lncRNAs), when combined with traditional anti-cancer medicines or radiotherapy, can improve efficacy and decrease mortality in cancer. Investigating the role of ferroptosis-related lncRNAs may help strategise new therapeutic options for breast cancer (BC). Herein, we briefly discuss the genes and pathways of ferroptosis involved in iron and reactive oxygen species (ROS) metabolism, including the XC −/GSH/GPX4 system, ACSL4/LPCAT3/15-LOX and FSP1/CoQ10/NAD(P)H pathways, and investigate the correlation between ferroptosis and LncRNA in BC to determine possible biomarkers related to ferroptosis.
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- 2024
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39. An increase in SNHG5 expression is associated with poor cancer prognosis, according to a meta-analysis
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Qiang Huang, Yi-gui Xia, Yong-jian Huang, Hai-feng Qin, Qun-xian Zhang, Chun-feng Wei, Wu-ru Tang, and Yuan Liao
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lncRNA ,SNHG5 ,Cancer ,Prognosis ,Meta-analysis ,Medicine - Abstract
Abstract Background He long noncoding RNA small nucleolar host RNA 5 (SNHG5) is highly expressed in many cancers, and there is a notable correlation between the elevated expression of SNHG5 and survival outcome in cancer patients. The objective of this study was to conduct a meta-analysis to evaluate the correlation between SNHG5 expression and the clinical outcome of cancer patients. Methods Six relevant electronic databases were exhaustively searched, and, depending on the inclusion and exclusion criteria, appropriate literature was obtained. The Newcastle-Ottawa Scale (NOS) score was utilized to evaluate the quality of the research for every article included, and pertinent data from each study were carefully extracted. Hazard ratios (HRs), odds ratios (ORs) and 95% confidence intervals (CIs) were combined to explore the association of SNHG5 expression levels with cancer prognosis, and sensitivity analyses and assessments of publication bias were also conducted to investigate any possibility in the publication of the studies. Results Eleven studies encompassing 721 patients were ultimately collected. When combined, the hazard ratios (HRs) revealed a substantial direct correlation between elevated SNHG5 expression and an unfavourable prognosis for cancer patients (HR = 1.90, 95% CI 0.87–4.15); however, the correlation did not reach statistical significance. Furthermore, high SNHG5 expression was predictive of advanced TNM stage (OR: 1.988, 95% CI 1.205–3.278) and larger tumour size (OR: 1.571, 95% CI 1.090–2.264); moreover, there were nonsignificant relationships between SNHG5 expression and DM (OR: 0.449, 95% CI 0.077–2.630), lymph node metastasis (OR: 1.443, 95% CI 0.709–2.939), histological grade (OR: 2.098, 95% CI 0.910–4.838), depth of invasion (OR: 1.106, 95% CI 0.376–3.248), age (OR: 0.946, 95% CI 0.718–1.247) and sex (OR: 0.762, 95% CI 0.521–1.115). Conclusion SNHG5 expression is typically increased in the majority of tumour tissues. Elevated SNHG5 expression may indicate poor prognosis in cancer patients. Therefore, SNHG5 is a promising potential therapeutic target for tumours and a reliable prognostic biomarker.
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- 2024
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40. Integration analysis of lncRNA and mRNA expression data identifies DOCK4 as a potential biomarker for elderly osteoporosis
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Chengai Wu, Chao Wang, Bin Xiao, Shan Li, Yueyang Sheng, Qianqian Wang, Jianfeng Tao, Yanzhuo Zhang, and Xu Jiang
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Elderly osteoporosis ,Diagnostic ,DOCK4 ,lncRNA ,miRNA ,Internal medicine ,RC31-1245 ,Genetics ,QH426-470 - Abstract
Abstract Background We aimed to identify some potential biomarkers for elderly osteoporosis (OP) by integral analysis of lncRNA and mRNA expression data. Methods A total of 8 OP cases and 5 healthy participants were included in the study. Fasting peripheral venous blood samples were collected from individuals, and total RNA was extracted. RNA-seq library was prepared and sequenced on the Illumina HiSeq platform. Differential gene expression analysis was performed using “DESeq2” package in R language. Functional enrichment analysis was conducted using the “clusterProfiler” package, and the cis- and trans-regulatory relationships between lncRNA and target mRNA were analyzed by the lncTar software. A protein-protein interaction (PPI) network was constructed using the STRING database, and hub genes were identified through the MCODE plugin in Cytoscape. Results We identified 897 differentially expressed lncRNAs (DELs) and 1366 differentially expressed genes (DEGs) between normal and OP samples. After co-expression network analysis and cis-trans regulatory genes analysis, we identified 69 candidate genes regulated by lncRNAs. Then we further screened 7 genes after PPI analysis. The target gene DOCK4, trans-regulated by two lncRNAs, was found to be significantly upregulated in OP samples. Additionally, 4 miRNAs were identified as potential regulators of DOCK4. The potential diagnostic value of DOCK4 and its two trans-regulatory lncRNAs was supported by ROC analysis, indicating their potential as biomarkers for OP. Conclusion DOCK4 is a potential biomarker for elderly osteoporosis diagnostic. It is identified to be regulated by two lncRNAs and four miRNAs.
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- 2024
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41. Transcriptome reveals the roles and potential mechanisms of lncRNAs in the regulation of albendazole resistance in Haemonchus contortus
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Xindi Chen, Tengyu Wang, Wenrui Guo, Xu Yan, Huilin Kou, Yu Yu, Chunxia Liu, Wa Gao, Wenlong Wang, and Rui Wang
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Haemonchus contortus ,Albendazole ,Drug resistance ,lncRNA ,ceRNA ,Biotechnology ,TP248.13-248.65 ,Genetics ,QH426-470 - Abstract
Abstract Background Haemonchus contortus (H. contortus) is the most common parasitic nematode in ruminants and is prevalent worldwide. H. contortus resistance to albendazole (ABZ) hinders the efficacy of anthelmintic drugs, but little is known about the molecular mechanisms that regulate this of drug resistance. Recent research has demonstrated that long noncoding RNAs (lncRNAs) can exert significant influence as pivotal regulators of the emergence of drug resistance. Results In this study, transcriptome sequencing was conducted on both albendazole-sensitive (ABZ-sensitive) and albendazole-resistant (ABZ-resistant) H. contortus strains, with three biological replicates for each group. The analysis of lncRNA in the transcriptomic data revealed that there were 276 differentially expressed lncRNA (DElncRNA) between strains with ABZ-sensitive and ABZ-resistant according to the criteria of |log2Foldchange|≥ 1 and FDR
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- 2024
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42. The therapeutically actionable long non-coding RNA ‘T-RECS’ is essential to cancer cells’ survival in NRAS/MAPK-driven melanoma
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Valentin Feichtenschlager, Linan Chen, Yixuan James Zheng, Wilson Ho, Martina Sanlorenzo, Igor Vujic, Eleanor Fewings, Albert Lee, Christopher Chen, Ciara Callanan, Kevin Lin, Tiange Qu, Dasha Hohlova, Marin Vujic, Yeonjoo Hwang, Kevin Lai, Stephanie Chen, Thuan Nguyen, Denise P Muñoz, Yoshinori Kohwi, Christian Posch, Adil Daud, Klemens Rappersberger, Terumi Kohwi-Shigematsu, Jean-Philippe Coppé, and Susana Ortiz-Urda
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T-RECS ,lncRNA ,Melanoma ,MAPK-pathway ,hnRNPA2/B1 ,Apoptosis ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Finding effective therapeutic targets to treat NRAS-mutated melanoma remains a challenge. Long non-coding RNAs (lncRNAs) recently emerged as essential regulators of tumorigenesis. Using a discovery approach combining experimental models and unbiased computational analysis complemented by validation in patient biospecimens, we identified a nuclear-enriched lncRNA (AC004540.4) that is upregulated in NRAS/MAPK-dependent melanoma, and that we named T-RECS. Considering potential innovative treatment strategies, we designed antisense oligonucleotides (ASOs) to target T-RECS. T-RECS ASOs reduced the growth of melanoma cells and induced apoptotic cell death, while having minimal impact on normal primary melanocytes. Mechanistically, treatment with T-RECS ASOs downregulated the activity of pro-survival kinases and reduced the protein stability of hnRNPA2/B1, a pro-oncogenic regulator of MAPK signaling. Using patient- and cell line- derived tumor xenograft mouse models, we demonstrated that systemic treatment with T-RECS ASOs significantly suppressed the growth of melanoma tumors, with no noticeable toxicity. ASO-mediated T-RECS inhibition represents a promising RNA-targeting approach to improve the outcome of MAPK pathway-activated melanoma.
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- 2024
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43. Blockade of the lncRNA-DOT1L-LAMP5 axis enhances autophagy and promotes degradation of MLL fusion proteins
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Tian-Qi Chen, Heng-Jing Huang, Shun-Xin Zhu, Xiao-Tong Chen, Ke-Jia Pu, Dan Wang, Yan An, Jun-Yi Lian, Yu-Meng Sun, Yue-Qin Chen, and Wen-Tao Wang
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lncRNA ,LAMP5-AS1 ,DOT1L ,LAMP5 ,Autophagy ,MLL leukemia ,Diseases of the blood and blood-forming organs ,RC633-647.5 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Mixed-lineage leukemia (MLL) fusion gene caused by chromosomal rearrangement is a dominant oncogenic driver in leukemia. Due to having diverse MLL rearrangements and complex characteristics, MLL leukemia treated by currently available strategies is frequently associated with a poor outcome. Therefore, there is an urgent need to identify novel therapeutic targets for hematological malignancies with MLL rearrangements. Methods qRT-PCR, western blot, and spearman correction analysis were used to validate the regulation of LAMP5-AS1 on LAMP5 expression. In vitro and in vivo experiments were conducted to assess the functional relevance of LAMP5-AS1 in MLL leukemia cell survival. We utilized chromatin isolation by RNA purification (ChIRP) assay, RNA pull-down assay, chromatin immunoprecipitation (ChIP), RNA fluorescence in situ hybridization (FISH), and immunofluorescence to elucidate the relationship among LAMP5-AS1, DOT1L, and the LAMP5 locus. Autophagy regulation by LAMP5-AS1 was evaluated through LC3B puncta, autolysosome observation via transmission electron microscopy (TEM), and mRFP-GFP-LC3 puncta in autophagic flux. Results The study shows the crucial role of LAMP5-AS1 in promoting MLL leukemia cell survival. LAMP5-AS1 acts as a novel autophagic suppressor, safeguarding MLL fusion proteins from autophagic degradation. Knocking down LAMP5-AS1 significantly induced apoptosis in MLL leukemia cell lines and primary cells and extended the survival of mice in vivo. Mechanistically, LAMP5-AS1 recruits the H3K79 histone methyltransferase DOT1L to LAMP5 locus, directly activating LAMP5 expression. Importantly, blockade of LAMP5-AS1-LAMP5 axis can represses MLL fusion proteins by enhancing their degradation. Conclusions The findings underscore the significance of LAMP5-AS1 in MLL leukemia progression through the regulation of the autophagy pathway. Additionally, this study unveils the novel lncRNA-DOT1L-LAMP5 axis as promising therapeutic targets for degrading MLL fusion proteins.
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- 2024
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44. Bioinformatic analysis and experimental validation of cuproptosis-related LncRNA as a novel biomarker for prognosis and immunotherapy of oral squamous cell carcinoma
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Shuang Liang, Lanting Ji, Zhenyuan Yu, YaHsin Cheng, Ruifang Gao, Wenpeng Yan, and Fang Zhang
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Cuproptosis ,lncRNA ,Oral squamous cell carcinoma ,Prognostic model ,Biomarkers ,Immune response ,Genetics ,QH426-470 - Abstract
Abstract Background The novel form of regulatory cell death, cuproptosis, is characterized by proteotoxicity, which ultimately leads to cell death. Its targeting has emerged as a promising therapeutic approach for oral squamous cell carcinoma (OSCC). Long noncoding RNAs (lncRNAs) participate in epigenetic regulation and have been linked to the progression, prognosis, and treatment of OSCC. Thus, this study aimed to identify new cuproptosis-related lncRNAs (CRLs), establish predictive models for clinical prognosis, immune response, and drug sensitivity, and provide novel insights into immune escape and tumor drug resistance. Methods The present study screened eight CRLs (THAP9-AS1, STARD4-AS1, WDFY3-AS2, LINC00847, CDKN2A-DT, AL132800.1, GCC2-AS1, AC005746.1) using Lasso Cox regression analysis to develop an eight-CRL prognostic model. Patients were categorized into high- and low-risk groups using risk scores. To evaluate the predictive ability of the model, Kaplan-Meier analysis, ROC curves, and nomograms were employed. Furthermore, the study investigated the differences in immune function and anticancer drug sensitivity between the high- and low-risk groups. To validate the expression of CRLs in the model, OSCC cell lines were subjected to quantitative real-time fluorescence PCR (qRT-PCR). Results The results of the study showed that the high-risk group had a shorter overall survival (OS) time in OSCC patients. Cox regression analysis demonstrated that the high-risk score was an independent risk factor for a poor prognosis. The validity of the model was confirmed using ROC curve analysis, and a nomogram was developed to predict the prognosis of OSCC patients. Furthermore, patients in the high-risk group with high TMB had a poorer prognosis. Patients in the low-risk group responded better to immunotherapy than those in the high-risk group. Additionally, the risk scores were significantly associated with drug sensitivity in OSCC patients. Finally, the findings of qRT-PCR supported the reliability of the proposed risk model. Conclusion The study identified and established the 8-CRL model, which represents a novel pathway of lncRNA regulation of cuproptosis in OSCC. This model provides guidance for the prognosis and treatment of OSCC and offers a new insight into immune escape and tumor drug resistance.
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- 2024
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45. LINC01559 promotes lung adenocarcinoma metastasis by disrupting the ubiquitination of vimentin
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Hao Feng, Dengfei Xu, Chenyang Jiang, Yuming Chen, Junru Wang, Zirui Ren, Xiang Li, Xu Dong Zhang, and Shundong Cang
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Lung adenocarcinoma ,lncRNA ,LINC01559 ,Vimentin ,Metastasis ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Abstract Background Distant metastasis is the major cause of lung adenocarcinoma (LUAD)-associated mortality. However, molecular mechanisms involved in LUAD metastasis remain to be fully understood. While the role of long non-coding RNAs (lncRNAs) in cancer development, progression, and treatment resistance is being increasingly appreciated, the list of dysregulated lncRNAs that contribute to LUAD pathogenesis is also rapidly expanding. Methods Bioinformatics analysis was conducted to interrogate publicly available LUAD datasets. In situ hybridization and qRT-PCR assays were used to test lncRNA expression in human LUAD tissues and cell lines, respectively. Wound healing as well as transwell migration and invasion assays were employed to examine LUAD cell migration and invasion in vitro. LUAD metastasis was examined using mouse models in vivo. RNA pulldown and RNA immunoprecipitation were carried out to test RNA–protein associations. Cycloheximide-chase assays were performed to monitor protein turnover rates and Western blotting was employed to test protein expression. Results The expression of the lncRNA LINC01559 was commonly upregulated in LUADs, in particular, in those with distant metastasis. High LINC01559 expression was associated with poor outcome of LUAD patients and was potentially an independent prognostic factor. Knockdown of LINC01559 diminished the potential of LUAD cell migration and invasion in vitro and reduced the formation of LUAD metastatic lesions in vivo. Mechanistically, LINC01559 binds to vimentin and prevents its ubiquitination and proteasomal degradation, leading to promotion of LUAD cell migration, invasion, and metastasis. Conclusion LINC01559 plays an important role in LUAD metastasis through stabilizing vimentin. The expression of LINC01559 is potentially an independent prognostic factor of LUAD patients, and LINC01559 targeting may represent a novel avenue for the treatment of late-stage LUAD.
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- 2024
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46. Integration of transcription regulation and functional genomic data reveals lncRNA SNHG6’s role in hematopoietic differentiation and leukemia
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Joshua M. Hazan, Raziel Amador, Tahleel Ali-Nasser, Tamar Lahav, Stav Roni Shotan, Miryam Steinberg, Ziv Cohen, Dvir Aran, David Meiri, Yehuda G. Assaraf, Roderic Guigó, and Assaf C. Bester
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lncRNA ,CRISPR screening ,Machine learning ,Gene regulation ,Hematopoiesis. ,Medicine - Abstract
Abstract Background Long non-coding RNAs (lncRNAs) are pivotal players in cellular processes, and their unique cell-type specific expression patterns render them attractive biomarkers and therapeutic targets. Yet, the functional roles of most lncRNAs remain enigmatic. To address the need to identify new druggable lncRNAs, we developed a comprehensive approach integrating transcription factor binding data with other genetic features to generate a machine learning model, which we have called INFLAMeR (Identifying Novel Functional LncRNAs with Advanced Machine Learning Resources). Methods INFLAMeR was trained on high-throughput CRISPR interference (CRISPRi) screens across seven cell lines, and the algorithm was based on 71 genetic features. To validate the predictions, we selected candidate lncRNAs in the human K562 leukemia cell line and determined the impact of their knockdown (KD) on cell proliferation and chemotherapeutic drug response. We further performed transcriptomic analysis for candidate genes. Based on these findings, we assessed the lncRNA small nucleolar RNA host gene 6 (SNHG6) for its role in myeloid differentiation. Finally, we established a mouse K562 leukemia xenograft model to determine whether SNHG6 KD attenuates tumor growth in vivo. Results The INFLAMeR model successfully reconstituted CRISPRi screening data and predicted functional lncRNAs that were previously overlooked. Intensive cell-based and transcriptomic validation of nearly fifty genes in K562 revealed cell type-specific functionality for 85% of the predicted lncRNAs. In this respect, our cell-based and transcriptomic analyses predicted a role for SNHG6 in hematopoiesis and leukemia. Consistent with its predicted role in hematopoietic differentiation, SNHG6 transcription is regulated by hematopoiesis-associated transcription factors. SNHG6 KD reduced the proliferation of leukemia cells and sensitized them to differentiation. Treatment of K562 leukemic cells with hemin and PMA, respectively, demonstrated that SNHG6 inhibits red blood cell differentiation but strongly promotes megakaryocyte differentiation. Using a xenograft mouse model, we demonstrate that SNHG6 KD attenuated tumor growth in vivo. Conclusions Our approach not only improved the identification and characterization of functional lncRNAs through genomic approaches in a cell type-specific manner, but also identified new lncRNAs with roles in hematopoiesis and leukemia. Such approaches can be readily applied to identify novel targets for precision medicine.
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- 2024
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47. Targeting of H19/cell adhesion molecules circuitry by GSK-J4 epidrug inhibits metastatic progression in prostate cancer
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Valeria Pecci, Fabiola Troisi, Aurora Aiello, Sara De Martino, Angela Carlino, Vincenzo Fiorentino, Cristian Ripoli, Dante Rotili, Francesco Pierconti, Maurizio Martini, Manuela Porru, Francesco Pinto, Antonello Mai, Pier Francesco Bassi, Claudio Grassi, Carlo Gaetano, Alfredo Pontecorvi, Lidia Strigari, Antonella Farsetti, and Simona Nanni
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lncRNA ,Metastasis ,Lysine demethylase ,Preclinical models ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Cytology ,QH573-671 - Abstract
Abstract Background About 30% of Prostate cancer (PCa) patients progress to metastatic PCa that remains largely incurable. This evidence underlines the need for the development of innovative therapies. In this direction, the potential research focus might be on long non-coding RNAs (lncRNAs) like H19, which serve critical biological functions and show significant dysregulation in cancer. Previously, we showed a transcriptional down-regulation of H19 under combined pro-tumoral estrogen and hypoxia treatment in PCa cells that, in turn, induced both E-cadherin and β4 integrin expression. H19, indeed, acts as transcriptional repressor of cell adhesion molecules affecting the PCa metastatic properties. Here, we investigated the role of H19/cell adhesion molecules circuitry on in vivo PCa experimental tumor growth and metastatic dissemination models. Methods H19 was silenced in luciferase-positive PC-3 and 22Rv1 cells and in vitro effect was evaluated by gene expression, proliferation and invasion assays before and after treatment with the histone lysine demethylase inhibitor, GSK-J4. In vivo tumor growth and metastasis dissemination, in the presence or absence of GSK-J4, were analyzed in two models of human tumor in immunodeficient mice by in vivo bioluminescent imaging and immunohistochemistry (IHC) on explanted tissues. Organotypic Slice Cultures (OSCs) from fresh PCa-explant were used as ex vivo model to test GSK-J4 effects. Results H19 silencing in both PC-3 and 22Rv1 cells increased: i) E-cadherin and β4 integrin expression as well as proliferation and invasion, ii) in vivo tumor growth, and iii) metastasis formation at bone, lung, and liver. Of note, treatment with GSK-J4 reduced lesions. In parallel, GSK-J4 efficiently induced cell death in PCa-derived OSCs. Conclusions Our findings underscore the potential of the H19/cell adhesion molecules circuitry as a targeted approach in PCa treatment. Modulating this interaction has proven effective in inhibiting tumor growth and metastasis, presenting a logical foundation for targeted therapy.
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- 2024
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48. lncRNA-MIAT rs9625066 polymorphism could be a potential biomarker for ischemic stroke
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Yin-Hua Weng, Jie Chen, Wen-Tao Yu, Yan-Ping Luo, Chao Liu, Jun Yang, and Hong-Bo Liu
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Ischemic stroke ,MIAT ,Polymorphism ,lncRNA ,rs9625066 ,Internal medicine ,RC31-1245 ,Genetics ,QH426-470 - Abstract
Abstract Background Ischemic stroke (IS) is a common and serious neurological condition that is highly fatal but so far no early diagnostic markers are available. Myocardial infarction-associated transcript (MIAT) is a long non-coding RNA (lncRNA) that could lead to IS by inducing autophagy and apoptosis in neuronal cells. However, there has been no report on the link between susceptibility to IS and the single-nucleotide polymorphisms (SNPs) of MIAT. This study aimed to investigate the association between MIAT gene polymorphisms and IS risk. Methods A total of 320 IS patients and 310 age-, sex- and race-matched controls were included in this study. Four polymorphisms (rs2157598, rs5761664, rs1894720, and rs9625066) were genotyped by using SNPscan technique. Results Among the 4 polymorphisms of MIAT, only rs9625066 was associated with IS risk (CA vs. CC: adjusted OR = 0.55, 95% CI, 0.37–0.85, P = 0.006; AA vs. CC: adjusted OR = 0.39, 95% CI, 0.16–0.94, P = 0.036; (AA + CA vs. CC: adjusted OR = 0.53, 95% CI, 0.35–0.80, P = 0.002; A vs. C adjusted OR = 0.59, 95% CI, 0.42–0.82, P = 0.002). Haplotype analysis showed a 1.32-fold increase (95% CI, 1.05–1.67, P = 0.017) in IS risk for rs2157598-rs5761664-rs1894720-rs9625066 (A-C-G-C). Logistic regression analysis identified some independent impact factors for IS including rs9625066 AA/AC, TC, TG, HDL-C (P
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- 2024
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49. RNA sequencing reveals differential long noncoding RNA expression profiles in bacterial and viral meningitis in children
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Xin Li, Suzhen Sun, and Huifeng Zhang
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Bacterial meningitis ,Viral meningitis ,lncRNA ,ceRNA ,Internal medicine ,RC31-1245 ,Genetics ,QH426-470 - Abstract
Abstract Background We aimed to investigate the involvement of long non-coding RNA (lncRNA) in bacterial and viral meningitis in children. Methods The peripheral blood of five bacterial meningitis patients, five viral meningitis samples, and five healthy individuals were collected for RNA sequencing. Then, the differentially expressed lncRNA and mRNA were detected in bacterial meningitis vs. controls, viral meningitis vs. healthy samples, and bacterial vs. viral meningitis patients. Besides, co-expression and the competing endogenous RNA (ceRNA) networks were constructed. Receiver operating characteristic curve (ROC) analysis was performed. Results Compared with the control group, 2 lncRNAs and 32 mRNAs were identified in bacterial meningitis patients, and 115 lncRNAs and 54 mRNAs were detected in viral meningitis. Compared with bacterial meningitis, 165 lncRNAs and 765 mRNAs were identified in viral meningitis. 2 lncRNAs and 31 mRNAs were specific to bacterial meningitis, and 115 lncRNAs and 53 mRNAs were specific to viral meningitis. The function enrichment results indicated that these mRNAs were involved in innate immune response, inflammatory response, and immune system process. A total of 8 and 1401 co-expression relationships were respectively found in bacterial and viral meningitis groups. The ceRNA networks contained 1 lncRNA-mRNA pair and 4 miRNA-mRNA pairs in viral meningitis group. GPR68 and KIF5C, identified in bacterial meningitis co-expression analysis, had an area under the curve (AUC) of 1.00, while the AUC of OR52K2 and CCR5 is 0.883 and 0.698, respectively. Conclusions Our research is the first to profile the lncRNAs in bacterial and viral meningitis in children and may provide new insight into understanding meningitis regulatory mechanisms.
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- 2024
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50. Identification of functional genes in liver fibrosis based on bioinformatics analysis of a lncRNA-mediated ceRNA network
- Author
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Feng Zhang, Siya Pei, and Meifang Xiao
- Subjects
Liver fibrosis ,Bioinformatics analysis ,lncRNA ,ceRNA ,Perl ,Internal medicine ,RC31-1245 ,Genetics ,QH426-470 - Abstract
Abstract Background Liver fibrosis is a major global healths problem; nevertheless, its molecular mechanism are not completely clear. This study aimed to build a lncRNA-miRNA-mRNA network, identify potentially related lncRNAs, and explore the pathogenesis of liver fibrosis. Materials and methods We used the Gene Expression Omnibus databases and bioinformatics analysis to identify differentially expressed genes (DEGs) between liver fibrosis and normal tissues. The ceRNA network was constructed according to the interactions between DElncRNA, miRNA, and DEmRNA. Then, these DEGs were identified using functional enrichment analysis, and a protein–protein interaction (PPI) network was established. The critical lncRNAs were verified using the quantitative real-time polymerase chain reaction (qRT-PCR). Results The ceRNA network was composed of three lncRNAs, five miRNAs, and 93 mRNAs. Gene Ontology functional enrichment analysis revealed significant enhancement in cell components, molecular function, and biological process. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed pathways associated with transcriptional misregulation in cancer, including the Rap1 signaling pathway, proteoglycans in cancer, mineral absorption, HTLV-l infection, and central carbon metabolism in cancer. According to the PPI network and the GSE84044 database, seven hub genes associated with liver fibrosis were identified. In addition, qRT-PCR revealed that lncRNA AC100861 (lncRNA TNFRSF10A-DT) was explicitly decreased in liver fibrosis tissues and activated hepatic stellate cells. Conclusions In summary, this study preliminarily found that lncRNA TNFRSF10A-DT may be a biomarker for the diagnosis and outcome of liver fibrosis. We uncovered a novel lncRNA-mediated ceRNA regulatory mechanism in the pathogenesis of liver fibrosis.
- Published
- 2024
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