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Abstract The redox status is intricately linked to the development and progression of cancer, a process that can be modulated by long non-coding RNAs (lncRNAs). Previous studies have demonstrated that redox regulation can be considered a potential therapeutic approach for cancer. However, the redox-related lncRNA predictive signature specific to bladder cancer (BCa) has yet to be fully elucidated. The purpose of our study is to establish a redox-related lncRNA signature to improve the prognostic prediction for BCa patients. To achieve this, we downloaded transcriptome and clinical data from the Cancer Genome Atlas (TCGA) database. Prognostic redox-related lncRNAs were identified through univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox regression analysis, resulting in the establishment of two risk groups. A comprehensive analysis corresponding to clinical features between high-risk and low-risk groups was conducted. Eight redox-related lncRNAs (AC018653.3, AC090229.1, AL357033.4, AL662844.4, AP003352.1, LINC00649, LINC01138, and MAFG-DT) were selected to construct the risk model. The overall survival (OS) in the high-risk group was worse than that in the low-risk group (p

Abstract Background Long non-coding RNA (lncRNA) plays a pivotal role in bone regeneration by interaction with microRNAs (miRNAs) and constructing a lncRNA-miRNA regulatory network. Objectives This research aimed to elucidate the role of lncRNA CASC11 in the delayed healing process of tibial fractures and to explore its potential regulatory mechanisms. Materials and methods The expression levels of CASC11 and miR-150-3p in serum samples were detected and the predictive capability of CASC11 regarding delayed healing in fracture patients. Furthermore, the study confirmed the accuracy of the binding sites between CASC11 and miR-150-3p. Subsequently, overexpression/interference plasmids of CASC11, along with overexpression plasmids co-transfected with both CASC11 and miR-150-3p, were systematically introduced into MC3T3-E1 cells to investigate their effects on the expression of osteogenic marker genes, as well as their influence on cellular proliferation and apoptosis. Results The expression levels of CASC11 were significantly elevated, while miR-150-3p levels were markedly decreased in individuals exhibiting delayed fracture healing (P

Abstract Background Infertility is a reproductive health problem that attracts worldwide attention. Polycystic ovary syndrome (PCOS) is a major cause of female infertility and patients with obesity and PCOS are particularly common in clinical practice. Long non-coding RNA (lncRNAs) are a functional core in cells that regulate gene expression, transcription, and chromatin modification processes, and participate in epigenetics, cell cycle, and cell differentiation. LncRNAs are assumed to play a role in the occurrence and development of PCOS; however, their specific mechanism of action remains to be elucidated. Methods High-throughput sequencing technology has been used to sequence and analyze lncRNAs in exosomes from the follicular fluid of patients with obesity and PCOS and those who underwent assisted reproductive therapy owing to male factors. Specific expression profiles of patients with obesity and PCOS were obtained and functional information analysis combined with a literature review were performed to screen for differentially expressed lncRNAs, which were validated using real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR). Results High-throughput sequencing analysis revealed that compared to normal patients with male infertility, patients with obesity and PCOS had a total of 20 lncRNAs with significant expression differences in follicular fluid exosomes. Among them, 17 lncRNAs were upregulated and three were downregulated. Functional analysis showed that differentially expressed genes were mainly enriched in “cell metabolism,” “cell adhesion,” and other aspects: related gene pathways mainly involved Huntington’s disease, Parkinson’s disease, spliceosomes, non-alcoholic fatty liver disease, and ribosomes. Verification of differentially expressed lncRNAs revealed that the expression of lncRNAs TPT1-AS1, PTOV1-AS1, PTPRG-AS1, and SNHG14 in follicular fluid exosomes was consistent with the sequencing results. Conclusion A preliminary differential expression profile of lncRNAs in exosomes of patients with obesity and PCOS was established by transcriptomic analysis of these individuals. Our bioinformatics analysis results may be applicable to further study of the impact mechanism involving obesity and PCOS. These differentially expressed lncRNAs maybe served as potential biomarkers for in-depth studies of the occurrence, development on Follicle quality and function for patients with PCOS in the future.

Abstract Preeclampsia (PE) is an important research subject in obstetrics. Nevertheless, the underlying mechanisms of PE remain elusive. PE-related expression datasets (GSE96983, GSE96984 and GSE24129) were downloaded from the Gene Expression Omnibus (GEO) database. Firstly, the differentially expressed messenger RNAs (DE-mRNAs), DE-microRNA (DE-miRNAs) and DE-long non-coding RNA (DE-lncRNAs) between PE and control cohorts were identified, and the ceRNA network was constructed. Then candidate hub genes were obtained through five algorithms by the protein-protein intersection (PPI) network of the mRNAs. Further, five hub genes were identified by receiver operating characteristic (ROC) curve and gene expression profiles: DAXX, EFNB1, NCOR2, RBBP4 and SOCS1. The function of 5 hub genes was analyzed and the interaction between drugs and hub genes was predicted. A total of 5 small molecule drugs were predicted, namely benzbromarone, 9,10-phenanthrenequinone, chembl312032, insulin and aldesleukin. AGAP2-AS1 was mainly located in exosome and cytoplasm. Agap2-as1-related regulatory subnetworks were extracted from ceRNA networks which included 41 mRNAs, 2 miRNAs and 1 lncRNA, including the regulated relationship pairs AGAP2-AS1-hsa-miR-497-5p-SRPRB, and AGAP2-AS1-hsa-miR-195-5p-RPL36. In summary, we constructed a competitive endogenous RNA (ceRNA) network to identify five potential biomarkers (DAXX, EFNB1, NCOR2, SOCS1 and RBBP4) of PE. The in-depth analysis of the AGAP2-AS1 regulatory network will help to uncover more important molecules closely related to PE and provide a scientific Reference.

Abstract Disulfidptosis is a novel programmed cell death mode that has been reported to play a role in oncogenesis. Increasing evidences suggest that the long non-coding RNAs (lncRNAs) play crucial roles in the initiation and progression of bladder cancer (BLCA). However, the role and prognostic value of disulfidptosis-related lncRNAs in BLCA remain unknown.The aim of this study was to construct and validate a disulfidptosis-related lncRNA risk model for predicting the prognosis of BLCA patients. A risk model consisting of 5 disulfidptosis-related lncRNAs was developed to predict the prognosis of BLCA patients. The overall survival (OS) of BLCA patients in the high-risk group was significantly shorter than that in the low-risk group (P

Abstract Long non-coding RNAs (lncRNAs) have a notable role in the diagnosis and prognosis of cancer. However, the associations between lncRNA-related hub genes (LRHGs) expression and the corresponding outcomes have not been fully understood in lung adenocarcinoma (LUAD). Here, a total of 71 patients diagnosed with LUAD and 60 healthy volunteers at The First Affiliated Hospital of Huzhou University from April, 2023 to December, 2023 were enrolled in the present study. A LRHGs model was established using least absolute shrinkage and selection operator analyses of The Cancer Genome Atlas-LUAD datasets. The underlying mechanisms of the LRHGs were investigated via Gene Set Enrichment Analysis and Gene Set Variation Analysis. Additionally, the diagnostic role of serum HOXD cluster antisense RNA 2 (HOXD-AS2) was assessed by receiver operating characteristic (ROC) curve analysis. Lastly, TCGA-LUAD samples were divided into high- and low-HOXD-AS2 expression groups based on the median expression. The associations between HOXD-AS2 expression and miR-4538 as well as Calmodulin-Dependent Protein Kinase Type II subunit Beta (CAMK2B) levels were conducted through Pearson correlation analysis. A comprehensive analysis identified 141 differentially expressed lncRNAs between 539 LUAD tissues and 59 normal samples. A prognostic marker for overall survival was established by constructing a predictive signature consisting of 9 LRHGs. Subsequently, 474 LUAD samples were categorized into a high or low-risk group based on the median of the risk score. An independent prognostic model was constructed to confirm the validity of this categorization. Further comparisons of the clinicopathological features and LRHG-related pathways were performed between the two groups. Examinations of LRHG expression in two LUAD clusters and of the association between LRHG expression and immune infiltration were also conducted. HOXD-AS2 expression was shown to be elevated in LUAD tissues compared with matched normal tissues, and the serum HOXD-AS2 level was also notably increased in LUAD samples compared with healthy controls. The results of the ROC analysis indicated that the sensitivity and specificity of HOXD-AS2 were higher than that of cytokeratin-19 fragment (CYFRA21-1), which is a serum marker for LUAD. Pearson analyses indicated that miR-4538 level was negatively associated with HOXD-AS2 expression, but CAMK2B level showed positive correlation in LUAD. The results of the present study therefore indicated that the constructed LRHG model, particularly HOXD-AS2, could independently diagnose and predict the prognosis of LUAD, which suggested the underlying mechanism of the HOXD-AS2/miR-4538/CAMK2B, and might offer efficient strategies for LUAD treatment.

Objective N6-methyladenosine (m6A) is the most prevalent methylation of mRNA and plays crucial roles in various physiological processes, including pigmentation. Yet, the regulatory mechanisms, including long noncoding RNAs (lncRNAs) m6A methylation contributing to pigmentation in sheep skin remains unclear. The purpose of this study was to identify potential lncRNAs and the m6A methylation of lncRNAs associated with pigmentation. Methods RNA-seq and MeRIP-seq were performed to study the expression of lncRNAs and the m6A methylation of lncRNAs in black and white sheep skin. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the consistency with the RNA-seq and MeRIP-seq data. Results We identified 168 differentially expressed lncRNAs between the two sheep skin colors. The differentially expressed lncRNAs enriched in the pathway of ECM-receptor interaction, Rap1 signaling pathway, and Non-homologous end-joining may play essential roles in pigmentation. We identified 577 m6A peaks and 617 m6A peaks in black and white sheep skin, respectively, among which 20 m6A peaks showed significant differences. The enriched motif in sheep skin was “GGACU”, which aligned with the consensus motif “RRACH” (R = A or G, H = A, C or U). Differently methylated lncRNAs enriched in PI3K-Akt signaling pathway and Wnt signaling pathway might participate in skin pigmentation. ENSOARG00020015168 was the unique lncRNA with high expression and methylation (Hyper-Up) in black sheep shin. A lncRNA-mRNA network was constructed, with pigmentation-related genes, such as PSEN2, CCND3, COL2A1, and ERCC3. Conclusion The m6A modifications of lncRNAs in black and white colored sheep skin were analyzed comprehensively, providing new candidates for the regulation of pigmentation.

Bi Lin,1 Chaohao Huang2 1Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Hepatological Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of ChinaCorrespondence: Chaohao Huang, Department of Hepatological Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China, Email kirbylin2010@sina.comPurpose: Acute pancreatitis (AP) is a common digestive disorder characterized by high morbidity and mortality. This study aims to uncover differentially expressed long noncoding RNAs (lncRNAs) and mRNAs, as well as related pathways, in the early stage of acute pancreatitis (AP), with a focus on the role of Neat1 in AP and severe acute pancreatitis (SAP).Methods: In this study, we performed high-throughput RNA sequencing on pancreatic tissue samples from three normal mice and three mice with cerulein-induced AP to describe and analyze the expression profiles of long non-coding RNAs (lncRNAs) and mRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted on the differentially expressed mRNAs to identify enriched pathways and biological processes. An lncRNA-miRNA-mRNA interaction network was constructed to elucidate potential regulatory mechanisms. Furthermore, we utilized Neat1 knockout mice to investigate the role of Neat1 in the pathogenesis of cerulein-AP and L-arginine-severe acute pancreatitis (SAP).Results: Our results revealed that 261 lncRNAs and 1522 mRNAs were differentially expressed in the cerulein-AP group compared to the control group. GO and KEGG analyses of the differentially expressed mRNAs indicated that the functions of the corresponding genes are enriched in cellular metabolism, intercellular structure, and positive regulation of inflammation, which are closely related to the central events in the pathogenesis of AP. A ceRNA network involving 5 lncRNAs, 226 mRNAs, and 61 miRNAs were constructed. Neat1 was identified to have the potential therapeutic effects in AP. Neat1 knockout in mice inhibited pyroptosis in both the AP/SAP mouse models.Conclusion: We found that lncRNAs, particularly Neat1, play a significant role in the pathogenesis of AP. This finding may provide new insights into further exploring the pathogenesis of SAP and could lead to the identification of new targets for the treatment of AP and SAP.Keywords: acute pancreatitis, lncRNA, ceRNA, NEAT1, pyroptosis

Abstract Long non-coding RNAs (lncRNAs) have emerged as pivotal regulators in numerous biological processes, including macrophage-mediated inflammatory responses, which play a critical role in the progress of diverse diseases. This study focuses on the regulatory function of lncRNA brain and reproductive organ-expressed protein (BRE) antisense RNA 1 (BRE-AS1) in modulating the inflammatory activation of monocytes/macrophages. Employing the THP-1 cell line as a model, we demonstrate that lipopolysaccharide (LPS) treatment significantly upregulates BRE-AS1 expression. Notably, specific knockdown of BRE-AS1 via siRNA transfection enhances LPS-induced expression of interleukin (IL)-6 and IL-1β, while not affecting tumor necrosis factor (TNF)-α levels. This selective augmentation of pro-inflammatory cytokine production coincides with increased phosphorylation of Janus kinase (JAK)2 and signal transducer and activator of transcription (STAT)3. Furthermore, BRE-AS1 suppression results in the downregulation of suppressor of cytokine signaling (SOCS)3, an established inhibitor of the JAK2/STAT3 pathway. Bioinformatics analysis identified binding sites for miR-30b-5p on both BRE-AS1 and SOCS3 mRNA. Intervention with a miR-30b-5p inhibitor and a synthetic RNA fragment that represents the miR-30b-5p binding site on BRE-AS1 attenuates the pro-inflammatory effects of BRE-AS1 knockdown. Conversely, a miR-30b-5p mimic replicated the BRE-AS1 attenuation outcomes. Our findings elucidate the role of lncRNA BRE-AS1 in modulating inflammatory activation in THP-1 cells via the miR-30b-5p/SOCS3/JAK2/STAT3 signaling pathway, proposing that manipulation of macrophage BRE-AS1 activity may offer a novel therapeutic avenue in diseases characterized by macrophage-driven pathogenesis.

Abstract Background Long noncoding RNAs (lncRNAs) have been recognized as viable prognostic and therapeutic indicators for numerous human malignancies. Nonetheless, the operational roles and fundamental mechanisms of important lncRNAs that impact esophageal squamous cell carcinoma (ESCC) remain predominantly obscure. Recently, lncRNAs have been identified to exert regulatory influence on epithelial-mesenchymal transition (EMT) via intricate interplay with EMT-associated transcription factors (TFs) and signaling pathways. The current experimental study aimed to elucidate the expression of four lncRNAs in ESCC patients and explain their potential involvement in the EMT process and the pathogenesis of ESCC. Methods In the study, the expression levels of lncRNAs (AGAP2-AS1, DLEU2, HMBOX1_1 (AC108449.2), and UGDH-AS1) and mRNAs (TWIST1, MMP13, and CD44S) between fifty ESCC and adjacent normal tissue samples were measured using quantitative real-time PCR. Results The upregulation of CD44S (36%), TWIST1 (52%), DLEU2 (58%), AGAP2-AS1 (62%), and MMP13 (74%), were indicated in ESCC samples, while the downregulation of UGDH-AS1 and HMBOX1_1 were found in 62% and 64% of patients, respectively. The expression levels of lncRNAs and EMT-related markers were found to be significantly correlated in several patient clinicopathological traits (P

Abstract Post-cardiac arrest brain (PCABI) is a severe medical condition characterized by a significant risk of neurological impairment and death. Nevertheless, the specific process and essential molecules responsible for its development are not fully understood. Profiling based on competing endogenous RNAs (ceRNA) has been implicated in the onset and progression of neurological disorders, yet its role in PCABI remains unclear. In this study, we performed RNA transcriptome sequencing analysis to identify differentially expressed genes in the rat model for cardiac arrest and cardiopulmonary resuscitation (CA/CPR). A hub ceRNA regulatory network was constructed using miRWalk 2.0 and Cytohubba plug-in in Cytoscape. Subsequently, real-time quantitative reverse transcription-polymerase chain reaction and dual-luciferase activity assays validated MSTRG.13,871, miR-155-5p, and Grip1 as differentially expressed in CA/CPR group, with MSTRG.13,871 capable of targeting both miR-155-5p and Grip1. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed the ceRNA network enrichment in immunoregulation mechanisms such as mitochondrion, apoptotic process, and negative regulation cell death. Our research highlights the mechanism of PCABI by revealing a critical regulatory axis involving MSTRG.13,871-miR-155-5p-Grip1 in the hippocampus CA1 region after CA/CPR in rats, proposing a feasible controlled mechanism, which may serve as a theoretical basis for designing innovative therapies.

Abstract Background Chronic heat stress (CHS) is a detrimental environmental stressor with a negative impact on the meat quality of broilers. However, the underlying mechanisms are not fully understood. This study investigates the effects of CHS on long non-coding RNA (lncRNA) expression and muscle injury in broilers, with a focus on its implications for meat quality. Results The results showed that CHS diminished breast muscle yield, elevated abdominal fat deposition, induced cellular apoptosis (P

Kangyi Hu, Haonan Wen, Ting Song, Zhixin Che, Yongjia Song, Min Song Clinical College of Traditional Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou, People’s Republic of ChinaCorrespondence: Min Song; Yongjia Song, Clinical College of Traditional Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou, 730000, People’s Republic of China, Email sm@gszy.edu.cn; syj@gszy.edu.cnAbstract: Long non-coding RNA (LncRNA), with transcripts over 200 nucleotides in length, play critical roles in numerous biological functions and have emerged as significant players in the pathogenesis of osteoarthritis (OA), an inflammatory condition traditionally viewed as a degenerative joint disease. This review comprehensively examines the influence of LncRNA on the inflammatory processes driving OA progression, focusing on their role in regulating gene expression, cellular activities, and inflammatory pathways. Notably, LncRNAs such as MALAT1, H19, and HOTAIR are upregulated in OA and exacerbate the inflammatory milieu by modulating key signaling pathways like NF-κB, TGF-β/SMAD, and Wnt/β-catenin. Conversely, LncRNA like MEG3 and GAS5, which are downregulated in OA, show potential in dampening inflammatory responses and protecting against cartilage degradation by influencing miRNA interactions and cytokine production. By enhancing our understanding of LncRNA’ roles in OA inflammation, we can better leverage them as potential biomarkers for the disease and develop innovative therapeutic strategies for OA management. This paper aims to delineate the mechanisms by which LncRNA influence inflammatory responses in OA and propose them as novel targets for therapeutic intervention.Keywords: osteoarthritis, LncRNA, inflammation, chondrocytes, pro-inflammatory factors

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.

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.

Abstract Necroptosis is intimately associated with the initiation and progression of colon adenocarcinoma (COAD). However, studies on necroptosis-related genes (NRGs) and the regulating long non-coding RNAs (NRGlncRNAs) in the context of COAD are limited. We retrieved the cancer genome atlas (TCGA) to collect datasets of NRGs and NRGlncRNAs on COAD patients. The risk model constructed using Cox and least absolute shrinkage and selection operator (LASSO) regression was then employed to identify NRGs and NRGlncRNAs with prognostic significance. Subsequently, we validated the results using gene expression omnibus (GEO) datasets from different populations, conducted Mendelian randomization (MR) analysis to explore the potential causal relationships between prognostic NRGs and COAD, and conducted cell experiments to verify the expression of prognostic NRGlncRNAs in COAD. Furthermore, we explored potential pathways and regulatory mechanisms of these prognostic NRGlncRNAs and NRGs in COAD through enrichment analysis, immune cell correlation analysis, tumor microenvironment analysis, immune checkpoint analysis, tumor sample clustering, and so on. We identified eight NRGlncRNAs (AC245100.5, AP001619.1, LINC01614, AC010463.3, AL162595.1, ITGB1-DT, LINC01857, and LINC00513) used for constructing the prognostic model and nine prognostic NRGs (AXL, BACH2, CFLAR, CYLD, IPMK, MAP3K7, ATRX, BRAF, and OTULIN) with regulatory relationships with them, and their validation was performed using GEO and GWAS datasets, as well as cell experiments, which showed largely consistent results. These prognostic NRGlncRNAs and NRGs modulate various biological functions, including immune inflammatory response, oxidative stress, immune escape, telomere regulation, and cytokine response, influencing the development of COAD. Additionally, stratified analysis of the high-risk and low-risk groups based on the prognostic model revealed elevated expression of immune cells, increased expression of tumor microenvironment cells, and upregulation of immune checkpoint gene expression in the high-risk group. Finally, through cluster analysis, we identified tumor subtypes, and the results of cluster analysis were essentially consistent with the analysis between risk groups. The prognostic NGRlncRNAs and NRGs identified in our study serve as prognostic indicators and potential therapeutic targets for COAD, providing a theoretical basis for the clinical diagnosis and treatment of COAD and offering guidance for further research.

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.

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.

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.

Hailei He,1 Zhen Wang,2 Cuilin Fang,3 Junfeng Yan4 1Department of Oral and Maxillofacial Surgery, Ganzhou People’s Hospital, Ganzhou, Jiangxi, 341000, People’s Republic of China; 2Department of Stomatology, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou, Zhejiang, 324000, People’s Republic of China; 3Department of Medicine and Equipment, Ganzhou Cancer Hospital, Ganzhou, Jiangxi, 341005, People’s Republic of China; 4Department of Stomatology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of ChinaCorrespondence: Junfeng Yan, Department of Stomatology, The First Affiliated Hospital of Nanchang University, No. 17, Yongwaizheng Street, Donghu District, Nanchang, Jiangxi, 330006, People’s Republic of China, Email yanjunfengd@163.comPurpose: LIPH4 has been identified as an oncogenic lncRNA in different malignant diseases. This research aims to elucidate the link between the expression of LIPH4 and its prognostic application in tongue squamous cell carcinoma (TSCC).Methods: To assess the expression of LIPH4, 142 TSCC and normal cases, respectively, which met the selection parameters, were used for qRT-PCR analysis. Furthermore, the association of LIPH4 expression with TSCC’s clinicopathological features was identified via the Chi-square test. Moreover, the Kaplan–Meier test was used for calculating the survival rates, whereas the association of patient survival with prognostic factors was assessed with the help of Cox proportional hazard analysis.Results: The data indicated upregulated LIPH4 levels in TSCC samples than healthy samples. Furthermore, LIPH4 expression was associated with TSCC differentiation and stage, where increased expression indicated reduced disease-free survival (DFS) and overall survival (OS) rates. Additionally, advanced TSCC individuals with enhanced LIPH4 expression had reduced OS and DFS rates than those with reduced LIPH4 expression. Serum LIPH4 could be a promising diagnostic bio-index for TSCC, with an area under the curve of 0.8920 (95% CI = 0.8540– 0.9299). These data revealed that the overexpression of LIPH4 might be a substantial prognostic factor for independently predicting the OS and DFS rates of TSCC patients.Conclusion: Altogether, this research revealed that the expression of LIPH4 expression is closely associated with TSCC progression and, therefore, can be employed as a biomarker for its prognosis.Keywords: lncRNA, LIPH4, biomarker, tongue squamous cell carcinoma (TSCC)

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.

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.

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.

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.

Abstract Breast cancer (BC) stands as a predominant global malignancy, significantly contributing to female mortality. Recently uncovered, histone lysine lactylation (kla) has assumed a crucial role in cancer progression. However, the correlation with lncRNAs remains ambiguous. Scrutinizing lncRNAs associated with Kla not only improves clinical breast cancer management but also establishes a groundwork for antitumor drug development. We procured breast tissue samples, encompassing both normal and cancerous specimens, from The Cancer Genome Atlas (TCGA) database. Utilizing Cox regression and XGBoost methods, we developed a prognostic model using identified kla-related lncRNAs. The model's predictive efficacy underwent validation across training, testing, and the overall cohort. Functional analysis concerning kla-related lncRNAs ensued. We identified and screened 8 kla-related lncRNAs to formulate the risk model. Pathway analysis disclosed the connection between immune-related pathways and the risk model of kla-related lncRNAs. Significantly, the risk scores exhibited a correlation with both immune cell infiltration and immune function, indicating a clear association. Noteworthy is the observation that patients with elevated risk scores demonstrated an increased tumor mutation burden (TMB) and decreased tumor immune dysfunction and exclusion (TIDE) scores, suggesting heightened responses to immune checkpoint blockade. Our study uncovers a potential link between Kla-related lncRNAs and BC, providing innovative therapeutic guidelines for BC management.

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.

Long non-coding RNAs (lncRNAs) are a group of transcripts longer than 200 nucleotides, which play important roles in regulating various cellular activities by the action of the RNA itself. However, about 40% of lncRNAs in human cells are potentially translated into micropeptides (also referred to as microproteins) usually shorter than 100 amino acids. Thus, these lncRNAs may function by both RNAs directly and their encoded micropeptides. The micropeptides encoded by lncRNAs may regulate transcription, translation, protein phosphorylation or degradation, or subcellular membrane functions. This review attempts to summarize the biochemical targets of the micropeptides-encoded by lncRNAs, which function by both RNAs and micropeptides, and discuss their associations with various diseases and their potentials as drug targets.

Cells produce short single-stranded non-coding RNAs (ncRNAs) called microRNAs (miRNAs), which actively regulate gene expression at the posttranscriptional level. Several miRNAs have been observed to exert significant impacts on bone health and bone-related disorders. One of these, miR-124, is observed in bone microenvironments and is conserved across species. It affects bone cell growth and differentiation by activating different transcription factors and signaling pathways. In-depth functional analyses of miR-124 have revealed several physiological and pathological roles exerted through interactions with other ncRNAs. Deciphering these RNA-mediated signaling networks and pathways is essential for understanding the potential impacts of dysregulated miRNA functions on bone biology. In this review, we aim to provide a comprehensive analysis of miR-124's involvement in bone physiology and pathology. We highlight the importance of miR-124 in controlling transcription factors and signaling pathways that promote bone growth. This review reveals therapeutic implications for the treatment of bone-related diseases.

Parasitic worms (helminths) establish chronic infection within mammalian hosts by strategically regulating their host’s immune responses. Deciphering the mechanisms by which host non-coding RNAs (ncRNA) co-ordinate the activation and regulation of immune cells is essential to understanding host immunity and immune-related pathology. It is also important to comprehend how pathogens secrete specific ncRNAs to manipulate gene expression of host immune cells and influence their response to infection. To investigate the contribution of both host and helminth derived ncRNAs to the activation and/or regulation of innate immune responses during a parasite infection, we examined ncRNA expression in the peritoneal macrophages from mice infected with Fasciola hepatica. We discovered the presence of several parasitic-derived miRNAs within host macrophages at 6 hrs and 18 hrs post infection. Target prediction analysis showed that these Fasciola miRNAs regulate host genes associated with the activation of host pro-inflammatory macrophages. Concomitantly, there was a distinct shift in host ncRNA expression, which was significant at 5 days post-infection. Prediction analysis suggested that these host ncRNAs target a different cohort of host genes compared to the parasite miRNAs, although the functional outcome was predicted to be similar i.e. reduced pro-inflammatory response and the promotion of a reparative/tolerant phenotype. Taken together, these observations uncover the interplay between host and parasitic ncRNAs and reveal a complementary regulation of the immune response that allows the parasite to evade immune detection and promote tissue repair for the host. These findings will provide a new understanding of the molecular interaction between parasites and host.

Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) have emerged as critical regulators in essentially all biological processes across eukaryotes. They exert their functions through chromatin remodeling, transcriptional regulation, interacting with RNA-binding proteins (RBPs), serving as microRNA sponges, etc. Although non-coding RNAs are typically more species-specific than coding RNAs, a number of well-characterized lncRNA (such as XIST and NEAT1) and circRNA (such as CDR1as and ciRS-7) are evolutionarily conserved. The studies on conserved lncRNA and circRNAs across multiple species could facilitate a comprehensive understanding of their roles and mechanisms, thereby overcoming the limitations of single-species studies. In this review, we provide an overview of conserved lncRNAs and circRNAs, and summarize their conserved roles and mechanisms.

We analyzed the structure of human long non-coding RNA (lncRNAs) genes to investigate whether the non-coding transcriptome is organized in modular domains, as is the case for protein-coding genes. To this aim, we compared all known human lncRNA exons and identified 340 pairs of exons with high sequence and/or secondary structure similarity but embedded in a dissimilar sequence context. We grouped these pairs in 106 clusters based on their reciprocal similarities. These shared modules are highly conserved between humans and the four great ape species, display evidence of purifying selection and likely arose as a result of recent segmental duplications. Our analysis contributes to the understanding of the mechanisms driving the evolution of the non-coding genome and suggests additional strategies towards deciphering the functional complexity of this class of molecules.

Background: Drug-induced liver injury (DILI) is a leading cause of drug development failures during clinical trials and post-market introduction. Current biomarkers, such as ALT and AST, lack the necessary specificity and sensitivity needed for accurate detection. Exosomes, which protect LncRNAs from RNase degradation, could provide reliable and easily accessible options for biomarkers. Materials and methods: RNA-sequencing was used to identify differentially expressed LncRNAs (DE-LncRNAs), followed by isolation of LncRNAs from plasma exosomes in this study. Exosome characterization was conducted by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot (WB). Bioinformatics analysis included functional enrichment and co-expression network analysis. Five rat models were established, and quantitative real-time PCR was used to verify the specificity and sensitivity of two candidate exosomal LncRNAs. Results: The APAP-induced hepatocellular injury model was successfully established for RNA-sequencing, leading to the identification of several differentially expressed exosomal LncRNAs. Eight upregulated exosomal DE-LncRNAs were selected for validation. Among them, NONRATT018001.2 (p

Long non-coding RNAs (LncRNAs) are a class of RNA molecules with nucleic acid lengths ranging from 200 bp to 100 kb that cannot code for proteins, which are diverse and widely expressed in both animals and plants. Scholars have found that lncRNAs can regulate human physiological processes at the gene and protein levels, mainly through the regulation of epigenetic, transcriptional and post-transcriptional levels of genes and proteins, as well as in the immune response by regulating the expression of immune cells and inflammatory factors, and thus participate in the occurrence and development of a variety of diseases. From the downstream targets of lncRNAs, we summarize the new research progress of lncRNA mechanisms other than miRNA sponges in recent years, aiming to provide new ideas and directions for the study of lncRNA mechanisms.

Chronic obstructive pulmonary disease (COPD) is the most prevalent chronic respiratory disorder that is becoming the leading cause of morbidity and mortality on a global scale. There is an unmet need to investigate the underlying pathophysiological mechanisms and unlock novel therapeutic avenues for COPD. Recent research has shed light on the significant roles played by diverse noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), in orchestrating the development and progression of COPD. This review provides an overview of the regulatory roles of ncRNAs in COPD, elucidating their underlying mechanisms, and illuminating the potential prospects of RNA-based therapeutics in the management of COPD.

The segmentally duplicated Pregnancy-specific glycoprotein (PSG) locus on chromosome 19q13 may be one of the most rapidly evolving in the human genome. It comprises ten coding genes (PSG1-9, 11) and one predominantly non-coding gene (PSG10) that are expressed in the placenta and gut, in addition to several poorly characterized long non-coding RNAs. We report that long non-coding RNA PSG8-AS1 has an oligodendrocyte-specific expression pattern and is co-expressed with genes encoding key myelin constituents. PSG8-AS1 exhibits two peaks of expression during human brain development coinciding with the most active periods of oligodendrogenesis and myelination. PSG8-AS1 orthologs were found in the genomes of several primates but significant expression was found only in the human, suggesting a recent evolutionary origin of its proposed role in myelination. Additionally, because co-deletion of chromosomes 1p/19q is a genomic marker of oligodendroglioma, expression of PSG8-AS1 was examined in these tumors. PSG8-AS1 may be a promising diagnostic biomarker for glioma, with prognostic value in oligodendroglioma.

LncRNA is a group of transcripts with a length exceeding 200 nucleotides that contribute to tumour development. Our research group found that LINC00052 expression was repressed during the formation of breast cancer (BC) multicellular spheroids. Intriguingly, LINC00052 precise role in BC remains uncertain. We explored LINC00052 expression in BC patients` RNA samples (TCGA) in silico, as well as in an in-house patient cohort, and inferred its cellular and molecular mechanisms. In vitro studies evaluated LINC00052 relevance in BC cells viability, cell cycle and DNA damage. Results. Bioinformatic RNAseq analysis of BC patients showed that LINC00052 is overexpressed in samples from all BC molecular subtypes. A similar LINC00052 expression pattern was observed in an in-house patient cohort. In addition, higher LINC00052 levels are related to better BC patient´s overall survival. Remarkably, MCF-7 and ZR-75-1 cells treated with estradiol showed increased LINC00052 expression compared to control, while these changes were not observed in MDA-MB-231 cells. In parallel, bioinformatic analyses indicated that LINC00052 influences DNA damage and cell cycle. MCF-7 cells with low LINC00052 levels exhibited increased cellular protection against DNA damage and diminished growth capacity. Furthermore, in cisplatin-resistant MCF-7 cells, LINC00052 expression was downregulated. Conclusion. This work shows that LINC00052 expression is associated with better BC patient survival. Remarkably, LINC00052 expression can be regulated by Estradiol. Additionally, assays suggest that LINC00052 could modulate MCF-7 cells growth and DNA damage repair. Overall, this study highlights the need for further research to unravel LINC00052 molecular mechanisms and potential clinical applications in BC.

Wool quality and yield are two important economic livestock traits. However, there are relatively few molecular studies on lncRNA for improving sheep wool, so these require further exploration. In this study, we examined skin tissue from the upper scapula of Super Merino (SM) and Small-Tailed Han (STH) sheep during the growing period. The apparent difference was verified via histological examination. High-throughput RNA sequencing identified differentially expressed (DE) long non-coding (lncRNAs) and messenger RNAs (mRNAs). The target gene of DE lncRNA and DE genes were enrichment analyzed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). A Reverse Transcription quantitative Polymerase Chain Reaction (RT-qPCR) was used to verify randomly selected DE lncRNAs and mRNAs. Finally, the DE, RAC2, WNT11, and FZD2 genes, which were enriched in the Wnt signaling pathway, were detected via immunohistochemistry. The results showed that a total of 20,888 lncRNAs and 31,579 mRNAs were identified in the skin tissues of the two sheep species. Among these, 56 lncRNAs and 616 mRNAs were differentially expressed. Through qRT-PCR, the trends in the randomly selected DE genes’ expression were confirmed to be aligned with the RNA-seq results. GO and KEGG enrichment analysis showed that DE lncRNA target genes were enriched in GO terms as represented by epidermal and skin development and keratin filature and in KEGG terms as represented by PI3K-Akt, Ras, MAPK, and Wnt signaling pathways, which were related to hair follicle growth and development. Finally, immunohistochemistry staining results indicated that RAC2, WNT11, and FZD2 were expressed in dermal papilla (DP). The lncRNAs MSTRG.9225.1 and MSTRG.98769.1 may indirectly participate in the regulation of hair follicle growth, development, and fiber traits by regulating their respective target genes, LOC114113396(KRTAP15-1), FGF1, and IGF1. In addition, MSTRG.84658.1 may regulate the Wnt signaling pathway involved in the development of sheep hair follicles by targeting RAC2. This study provides a theoretical reference for improving sheep breeding in the future and lays a foundation for further research on the effects of MSTRG.84658.1 and the target gene RAC2 on dermal papilla cells (DPC).

Abstract Yaks live in the Qinghai-Tibet Plateau for a long time where oxygen is scarce, but can ensure the smooth development of testis and spermatogenesis. The key lies in the functional regulation of the Sertoli cells under hypoxia. In this study, we sequenced yak Sertoli cells cultured in normal oxygen concentration (Normoxia) and treated with low oxygen concentration (Hypoxia) by whole transcriptomics, and screened out 194 differentially expressed mRNAs (DEmRNAs), 934 differentially expressed LncRNAs (DELncRNAs) and 129 differentially expressed miRNAs (DEmiRNAs). GO and KEGG analysis showed that these differential genes were mainly concentrated in PI3K-AKT, MAPK, RAS, and other signaling pathways, and were associated with glucose metabolism, tight junction, steroid hormone synthesis, cell fusion, and immunity of yak Sertoli cells. We constructed the gene interaction network of yak Sertoli cells in hypoxia and screened out the relationship pairs related to glucose metabolism and tight junction. The results suggested that the changes in energy metabolism, tight junction, and immune regulation of yak Sertoli cells under hypoxia might provide favorable conditions for spermatogenesis. This study provides data for further study on the role of non-coding RNA in testis development and spermatogenesis of yak.

Abstract Cadmium, a common metal pollutant, has been demonstrated to induce type 2 diabetes by disrupting pancreatic β cells function. In this study, transcriptome microarray was utilized to identify differential gene expression in oxidative damage to pancreatic β cells following cadmium exposure. The results indicated that a series of mRNAs, LncRNAs, and miRNAs were altered. Of the differentially expressed miRNAs, miR-29a-3p exhibited the most pronounced alteration, with an 11.62-fold increase relative to the control group. Following this, the target gene of miR-29a-3p was identified as Col3a1 through three databases (miRDB, miRTarbase and Tarbase), which demonstrated a decrease across the transcriptome microarray. The upstream target gene of miR-29a-3p was identified as NONMMUT036805, with decreased expression observed in the microarray. Finally, the expression trend of NONMMUT036805/miR-29a-3p/Col3a1 was reversed following NAC pretreatment. This was accompanied by a reduction in oxidative damage indicators, MDA/ROS/GSH-Px appeared to be negatively affected to varying degrees. In conclusion, this study has demonstrated that multiple RNAs are altered during cadmium exposure-induced oxidative damage in pancreatic β cells. The NONMMUT036805/miR-29a-3p/Col3a1 axis has been shown to be involved in this process, which provides a foundation for the identification of potential targets for cadmium toxicity intervention.

Abstract Background Studies have indicated a close association between genes linked to liquid–liquid phase separation (LLPS) and the progression of prostate cancer (PCa). However, the interplay among long non-coding RNAs (lncRNAs) linked to LLPS in PCa remains elusive. Therefore, we constructed a prediction model based on LLPS-related LncRNA in PCa to explore its relationship with the prognosis and drug treatment of PCa. Methods We obtained clinical and sequencing data from TCGA and LLPS genes from the Phase Separation Protein Database. By analyzing the differential expression of LLPS-related genes and lncRNAs in prostate cancer, and using Poisson correlation, we identified LLPS-related lncRNAs. Prognostic LLPS-lncRNAs were found through prognostic correlation analysis and included in a Cox model to compute regression coefficients. Patients were scored and divided into high- and low-risk groups. Independent prognostic factors were integrated into a prognostic nomogram with risk and Gleason scores. We also conducted drug sensitivity analyses, GSEA, and validated the impact of key lncRNAs through functional experiments. Results Our study identified five LLPS-associated lncRNAs that are of prognostic importance. And found notable disparities in biochemical recurrence rates and survival outcomes between these risk groups, with the low-risk cohort exhibiting superior prognostic indicators. Moreover, our prediction nomogram demonstrated robust predictive accuracy and significant clinical utility. Furthermore, our model exhibited promising capabilities in forecasting patient sensitivity to various conventional therapeutic drugs, thereby highlighting its potential in personalized treatment strategies. GSEA showed that these lncRNAs may influence PCa prognosis and sensitivity to therapeutic agents by affecting pathways such as cell cycle. Knockdown of AC009812.4 could inhibit the ability of PCa cells to proliferate, migrate and invade, and compare to paracancerous tissue, AC009812.4 in PCa tissue has significantly higher expression. Conclusion Our research uncovers the prognostic significance of lncRNAs associated with LLPS in PCa and established a model exhibiting excellent predictive accuracy for prognosis. Those lncRNAs may influence progress of PCa as well as sensitivity to therapy drugs through pathways such as cell cycle.

Abstract Gastric cancer remains a significant health challenge despite advancements in diagnosis and treatment. Early detection is critical to reducing mortality, necessitating the investigation of molecular mechanisms underlying gastric cancer progression. This study focuses on BRD4 expression and its correlation with miR-26a-3p, DLG5-AS1, and JMJD1C-AS1 lncRNAs in gastric cancer. Analysis of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets revealed significant upregulation of BRD4 in gastric cancer tissues compared to normal tissues, correlating negatively with miR-26a-3p and positively with DLG5-AS1 and JMJD1C-AS1 lncRNAs. Quantitative RT-PCR confirmed these findings in 25 gastric cancer tissue samples and 25 normal samples. BRD4's overexpression was associated with reduced survival rates and older patient age. MiR-26a-3p, a known tumor suppressor, showed decreased expression in gastric cancer tissues, with ROC analysis suggesting it, alongside BRD4, as a potential diagnostic biomarker. Additionally, bioinformatics predicted miR-26a-3p’s interaction with BRD4 mRNA. Upregulated lncRNAs DLG5-AS1 and JMJD1C-AS1 likely act as competing endogenous RNAs, sponging miR-26a-3p, thus promoting BRD4 dysregulation. These lncRNAs have not been previously studied in gastric cancer. The findings propose a novel BRD4/lncRNA/miRNA regulatory axis in gastric cancer, highlighting the potential of BRD4, DLG5-AS1, and JMJD1C-AS1 as biomarkers for early diagnosis. Further studies with larger sample sizes and in vivo and in vitro experiments are needed to elucidate this regulatory mechanism’s role in gastric cancer progression.

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.

Abstract Programmed cell death (PCD) is a process that eliminates infected, damaged, or possibly neoplastic cells to sustain homeostatic multicellular organisms. Although long noncoding RNAs (lncRNAs) are involved in various types of PCD and regulate tumor growth, invasion, and migration, the role of PCD-related lncRNAs in bladder cancer still lacks systematic exploration. In this research, we integrated multiple types of PCD as pan-PCD and identified eight pan-PCD-related lncRNAs (LINC00174, HCP5, HCG27, UCA1, SNHG15, GHRLOS, CYB561D2, and AGAP11). Then, we generated a pan-PCD-related lncRNA prognostic signature (PPlncPS) with excellent predictive power and reliability, which performed equally well in the E-MTAB-4321 cohort. In comparison with the low-PPlncPS score group, the high-PPlncPS score group had remarkably higher levels of angiogenesis, matrix, cancer-associated fibroblasts, myeloid cell traffic, and protumor cytokine signatures. In addition, the low-PPlncPS score group was positively correlated with relatively abundant immune cell infiltration, upregulated expression levels of immune checkpoints, and high tumor mutation burden (TMB). Immunogenomic profiles revealed that patients with both low PPlncPS scores and high TMB had the best prognosis and may benefit from immune checkpoint inhibitors. Furthermore, for patients with high PPlncPS scores, docetaxel, staurosporine, and luminespib were screened as potential therapeutic candidates. In conclusion, we generated a pan-PCD-related lncRNA signature, providing precise and individualized prediction for clinical prognosis and some new insights into chemotherapy and immune checkpoint inhibitor therapy for bladder cancer.

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.

Abstract Limited treatment options and poor prognosis present significant challenges in the treatment of lung squamous cell carcinoma (LUSC). Disulfidptosis impacts cancer progression and prognosis. We developed a prognostic signature using disulfidptosis-related long non-coding RNAs (lncRNAs) to predict the prognosis of LUSC patients. Gene expression matrices and clinical information for LUSC were downloaded from the TCGA database. Co-expression analysis identified 209 disulfidptosis-related lncRNAs. LASSO-Cox regression analysis identified nine key lncRNAs, forming the basis for establishing a prognostic model. The model’s validity was confirmed by Kaplan–Meier and ROC curves. Cox regression analysis identified the risk score (RS) as an independent prognostic factor inversely correlated with overall survival. A nomogram based on the RS demonstrated good predictive performance for LUSC patient prognosis. The relationship between RS and immune function was explored using ESTIMATE, CIBERSORT, and ssGSEA algorithms. According to the TIDE database, a negative correlation was found between RS and immune therapy responsiveness. The GDSC database revealed that 49 drugs were beneficial for the low-risk group and 25 drugs for the high-risk group. Silencing C10orf55 expression in SW900 cells reduced invasiveness and migration potential. In summary, this lncRNA model based on TCGA-LUSC data effectively predicts prognosis and assists clinical decision-making.

Abstract Prostate cancer remains a complex and challenging disease, necessitating innovative approaches for prognosis and therapeutic guidance. This study integrates machine learning techniques to develop a novel mitophagy-related long non-coding RNA (lncRNA) signature for predicting the progression of prostate cancer. Leveraging the TCGA-PRAD dataset, we identify a set of four key lncRNAs and formulate a riskscore, revealing its potential as a prognostic indicator. Subsequent analyses unravel the intricate connections between riskscore, immune cell infiltration, mutational landscapes, and treatment outcomes. Notably, the pan-cancer exploration of YEATS2-AS1 highlights its pervasive impact, demonstrating elevated expression across various malignancies. Furthermore, drug sensitivity predictions based on riskscore guide personalized chemotherapy strategies, with drugs like Carmustine and Entinostat showing distinct suitability for high and low-risk group patients. Regression analysis exposes significant correlations between the mitophagy-related lncRNAs, riskscore, and key mitophagy-related genes. Molecular docking analyses reveal promising interactions between Cyclophosphamide and proteins encoded by these genes, suggesting potential therapeutic avenues. This comprehensive study not only introduces a robust prognostic tool but also provides valuable insights into the molecular intricacies and potential therapeutic interventions in prostate cancer, paving the way for more personalized and effective clinical approaches.

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

Abstract Objective To investigate circadian rhythm-associated long non-coding RNA (lncRNA) signatures in predicting prognosis, metabolism, and immune infiltration in Head and Neck Squamous Cell Carcinoma (HNSC). Methods HNSC samples were collected from the TCGA database. A signature was constructed using Cox regression and Least Absolute Shrinkage and Selection Operator (LASSO) methods. The immune cell infiltration was analyzed using CIBERSORT, ssGSEA, and MCPcounter. The RT-qPCR was used to detect the expression of signature lncRNAs. Results A signature comprising 8 lncRNAs was constructed. The constructed signature demonstrated good prognostic prediction capability for HNSC. A nomogram encompassing risk score accurately predicted the long-term OS probability of HNSC. The infiltration levels of T cell, B cell and Macrophages were significantly higher in the high-risk group than in the low-risk group. Cluster analysis showed that the signature lncRNAs could classify the HNSC samples into two clusters. The RT-qPCR suggested that the expression of lncRNAs in signature was consistent with the data in TCGA. Conclusion The circadian rhythm-associated lncRNA signature has potential as a prognostic indicator for HNSC. It exhibits associations with metabolism, immune microenvironment, and drug sensitivity, thereby providing valuable insights for informing the treatment of HNSC.

Abstract Long non-coding RNAs (lncRNAs) have emerged as important players in cancer progression. Cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer with increasing incidence worldwide. The prognosis of the metastatic cSCC is poor, and currently there are no established biomarkers to predict metastasis risk or specific therapeutic targets for advanced or metastatic cSCC. To elucidate the role of lncRNAs in cSCC, RNA sequencing of patient derived cSCC cell lines and normal human epidermal keratinocytes was performed. The correlation analysis of differentially expressed lncRNAs and protein-coding genes revealed six distinct gene clusters with one of the upregulated clusters featuring genes associated with cell motility. Upregulation of the expression of lncRNAs linked to cSCC cell motility in cSCC and head and neck SCC (HNSCC) cells was confirmed using qRT-PCR. Elevated expression of HOTTIP and LINC00543 was also noted in SCC tumors in vivo and was associated with poorer prognosis in HNSCC and lung SCC cohorts within TCGA data, respectively. Altogether, these findings uncover a novel set of lncRNAs implicated in cSCC cell locomotion. These lncRNAs may serve as potential novel biomarkers and as putative therapeutic targets for locally advanced and metastatic cSCC.

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.