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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.

Background: Inflammatory cytokines such as Interleukin 1β(IL1β), IL6,Tumor Necrosis Factor-α (TNF-α) can inhibit osteoblast differentiation and induce osteoblast apoptosis. PANoptosis, a newly identified type of programmed cell death (PCD), may be influenced by long noncoding RNA (lncRNAs) which play important roles in regulating inflammation. However, the potential role of lncRNAs in inflammation and PANoptosis during osteogenic differentiation remains unclear. This study aimed to investigate the regulatory functions of lncRNAs in inflammation and apoptosis during osteogenic differentiation. Methods and results: High-throughput sequencing was used to identify differentially expressed genes involved in osteoblast differentiation under inflammatory conditions. Two lncRNAs associated with inflammation and PANoptosis during osteogenic differentiation were identified from sequencing data and Gene Expression Omnibus (GEO) databases. Their functionalities were analyzed using diverse bioinformatics methodologies, resulting in the construction of the lncRNA-miRNA-mRNA network. Among these, lncRNA (MIR17HG) showed a high correlation with PANoptosis. Bibliometric methods were employed to collect literature data on PANoptosis, and its components were inferred. PCR and Western Blotting experiments confirmed that lncRNA MIR17HG is related to PANoptosis in osteoblasts during inflammation. Conclusions: Our data suggest that TNF-α-induced inhibition of osteogenic differentiation and PANoptosis in MC3T3-E1 osteoblasts is associated with MIR17HG. These findings highlight the critical role of MIR17HG in the interplay between inflammation, PANoptosis, and osteogenic differentiation, suggesting potential therapeutic targets for conditions involving impaired bone formation and inflammatory responses. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common cancer in women and the leading cause of female deaths by cancer in the world worldwide. Hence, understanding the molecular mechanisms associated with breast cancer development and progression, including drug resistance and breast cancer metastasis, is essential for achieving the best management of breast cancer patients. Cancer-related long noncoding RNAs have been shown to be involved in the regulation of each stage of breast cancer progression. Additionally, exosomes are extracellular microvesicles that are central to intercellular communication and play an important role in tumorigenesis. Exosomes can be released from primary tumor cells into the bloodstream and transmit cellular signals to distant body sites. In this work, we review the findings regarding the cellular mechanisms regulated by exosomal lncRNAs that are essentials to chemoresistance development and metastasis of breast cancer. Likewise, we evaluate the outcomes of the potential clinical use of exosomal lncRNAs as breast cancer biomarkers to achieve personalized management of the patients. This finding highlights the importance of transcriptomic analysis of exosomal lncRNAs to understand the breast cancer tumorigenesis as well as to improve the clinical tests available for this disease. [ABSTRACT FROM AUTHOR]

Platinum-based chemotherapy has been widely used for clinical cancer treatment, but drug resistance is the main barrier to induce the poor prognosis of cancer patients. Long non-coding RNAs (lncRNAs) have been recognized as a type of new cancer therapeutic targets due to their important role in regulating cancer progression such as drug resistance. However, it is still challenged to effectively intervene the expression of lncRNAs as they are usually located at various subcellular organelles (e.g., nucleus, mitochondrion, and endoplasmic reticulum). We herein developed an endosomal pH-responsive nanoparticle (NP) platform for small interfering RNA (siRNA) and cisplatin prodrug co-delivery and effective cisplatin-resistant hepatocellular carcinoma (HCC) therapy. This co-delivery nanoplatform is comprised of a hydrophilic polyethylene glycol (PEG) shell and a hydrophobic poly (2-(diisopropylamino) ethyl methacrylate) (PDPA) core, in which cisplatin prodrug and electrostatic complexes of nucleus-targeting amphiphilic peptide (NTPA) and siRNA are encapsulated. After intravenous injection and then uptake by tumor cells, the endosomal pH could trigger the dissociation of nanoplatform and enhance the endosomal escape of loaded cisplatin prodrug and NTPA/siRNA complexes via the "proton sponge" effect. Subsequently, the NTPA/siRNA complexes could specifically transport siRNA into the nucleus and efficiently reverse cisplatin resistance via silencing the expression of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (lncMALAT1) mainly localized in the nucleus, ultimately inhibiting the growth of cisplatin-resistant HCC tumor. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

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 FROM AUTHOR]

Long noncoding RNAs (lncRNAs) constitute a distinctive subset of RNA molecules with limited protein-coding potential, which exert crucial impacts on various biological activities. In the context of cancer, dysregulated lncRNAs function as essential regulators that affect tumor initiation and malignant progression. These lncRNAs serve as competitive endogenous RNAs (ceRNAs) through sponging microRNAs and regulating the expression of targeted genes. Moreover, they also directly bind to RNA-binding proteins, which can be integrated into a complex mechanistic network. E2F1, an extensively studied transcription factor, mediates multiple malignant behaviors by regulating cell cycle progression, tumor metastasis, and therapeutic response. Emerging evidence suggests that lncRNAs play a pivotal role in regulating the E2F1 pathway. This review aims to elucidate the intricate gene regulatory programs between lncRNAs and E2F1 in cancer progression. We elaborate on distinct mechanistic networks involved in cancer progression, emphasizing the potential of the lncRNAs/E2F1 axes as promising targets for cancer therapy. Additionally, we provide novel perspectives on current evidence, limitations, and future directions for targeting lncRNAs in human cancers. Fully deciphering the intricate network of lncRNA/E2F1-mediated regulatory mechanisms in cancer could facilitate the translation of current findings into clinical course, such efforts ultimately significantly improve the clinical prognosis of cancer patients. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

Cell-matrix interactions in 3D environments significantly differ from those in 2D cultures. As such, mechanisms of mechanotransduction in 2D cultures are not necessarily applicable to cell-encapsulating hydrogels that resemble features of tissue architecture. Accordingly, the characterization of molecular pathways in 3D matrices is expected to uncover insights into how cells respond to their mechanical environment in physiological contexts, and potentially also inform hydrogel-based strategies in cell therapies. In this study, a bone marrow-mimetic hydrogel was employed to systematically investigate the stiffness-responsive transcriptome of mesenchymal stromal cells. High matrix rigidity impeded integrin-collagen adhesion, resulting in changes in cell morphology characterized by a contractile network of actin proximal to the cell membrane. This resulted in a suppression of extracellular matrix-regulatory genes involved in the remodeling of collagen fibrils, as well as the upregulation of secreted immunomodulatory factors. Moreover, an investigation of long noncoding RNAs revealed that the cytoskeleton regulator RNA (CYTOR) contributes to these 3D stiffness-driven changes in gene expression. Knockdown of CYTOR using antisense oligonucleotides enhanced the expression of numerous mechanoresponsive cytokines and chemokines to levels exceeding those achievable by modulating matrix stiffness alone. Taken together, our findings further our understanding of mechanisms of mechanotransduction that are distinct from canonical mechanotransductive pathways observed in 2D cultures. [ABSTRACT FROM AUTHOR]

Tumor growth and metastasis rely on angiogenesis. In recent years, long non-coding RNAs have been shown to play an important role in regulating tumor angiogenesis. Here, we review the multidimensional modes and relevant molecular mechanisms of long non-coding RNAs in regulating tumor angiogenesis. In addition, we summarize new strategies for tumor anti-angiogenesis therapies by targeting long non-coding RNAs. The aim of this study is to provide new diagnostic targets and treatment strategies for anti-angiogenic tumor therapy. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs), defined as RNA molecules exceeding 200 nucleotides in length, have been implicated in the regulation of various biological processes and the progression of tumors. Among them, LINC00518, a recently identified lncRNA encoded by a gene located on chromosome 6p24.3, consists of three exons and is predicted to positively regulate the expression of specific genes. LINC00518 has emerged as a key oncogenic lncRNA in multiple cancer types. It exerts its tumor-promoting effects by modulating the expression of several target genes, primarily through acting as a sponge for microRNAs (miRNAs). Additionally, LINC00518 influences critical signaling pathways, including the Wnt/β-catenin, JAK/STAT, and integrin β3/FAK pathways. Elevated levels of LINC00518 in tumor tissues are associated with increased tumor size, advanced clinical stage, metastasis, and poor survival prognosis. This review provides a comprehensive summary of the genetic characteristics, expression patterns, biological functions, and underlying mechanisms of LINC00518 in human diseases. [ABSTRACT FROM AUTHOR]

Introduction: Transient receptor potential (TRP) channels function as cellular sensors with a broad impact, and their dysregulation is linked to numerous cancers. The influence of TRP channel-related long noncoding RNAs (TCRLs) on uveal melanoma (UM) remains poorly understood. Methods: We employed bioinformatics to examine the RNA-seq data and relevant clinical information of UM in the TCGA databases. By implementing coexpression analysis, we identified differentially expressed TCRLs. Using univariate Cox regression analysis, selection operator (LASSO) algorithm and stepwise regression, five key prognostic biomarkers were chosen. The high- and low-risk groups were divided based on the risk scores. Afterwards, the prediction performance of the signature was evaluated by receiver operating characteristic (ROC) curve and Kaplan-Meier (K-M) survival analysis. The functional enrichment analysis of TCRLs was also investigated. Following that, we examined immune cell infiltration, immune checkpoint expression, and tumor immune microenvironment between patients in high and low risk groups. TCRLs were validated using Random forests and multifactor Cox analysis. Candidate biomarkers were identified and screened. Finally, the effects of the candidate biomarkers on the proliferation, migration and invasion of UM cells were detected by CCK-8 assay, migration assay and perforation invasion assay. Results: The risk score generated by five TCRLs demonstrated robust predictive power. The high-risk group exhibited a poorer prognosis, increased immune cell infiltration, and an active tumor immune microenvironment compared to the low-risk group. Furthermore, two TCRLs of risk score, AC092535.4 and LINC01637, were screened to multiplex modelling. The in vitro experiments demonstrated that UM cells were suppressed following AC092535.4 or LINC01637 knockdown. Discussion: Two TCRLs, AC092535.4 and LINC01637, serve as novel prognostic biomarkers for uveal melanoma and may present potential therapeutic targets. [ABSTRACT FROM AUTHOR]

In late 2019, the SARS-CoV-2 virus emerged as the cause of COVID-19, triggering a worldwide pandemic of unprecedented scale. A detailed comprehension is being established to elucidate the severe immunopathological condition in critical cases of COVID-19. Noncoding RNAs (ncRNAs) are the transcribed but untranslated part of the genome that used to be ignored or disregarded until recent times. The latest research has revealed the intricate role played by the immune system in responding to SARS-CoV-2 and the development of COVID-19, affecting important aspects such as cytokine storm syndrome, changes in blood clotting, attraction of immune cells, and regulation of blood vessels. Exploring the possibilities of host–virus RNA interactions and RNA-RBP interactions has garnered significant interest. Following SARS-CoV-2 infection, the levels of certain ncRNAs change to indirectly control the expression of antiviral genes and viral gene replication. Certain ncRNAs are utilized by SARS-CoV-2 to assist the virus in evading the immune system by reducing the production of type I interferon (IFN-1) and regulating cytokine levels. [ABSTRACT FROM AUTHOR]

Extranuclear localization of long noncoding RNAs (lncRNAs) is poorly understood. Based on machine learning evaluations, we propose a lncRNA-mitochondrial interaction pathway where polynucleotide phosphorylase (PNPase), through domains that provide specificity for primary sequence and secondary structure, binds nuclear-encoded lncRNAs to facilitate mitochondrial import. Using FVB/NJ mouse and human cardiac tissues, RNA from isolated subcellular compartments (cytoplasmic and mitochondrial) and cross-linked immunoprecipitate (CLIP) with PNPase within the mitochondrion were sequenced on the Illumina HiSeq and MiSeq, respectively. lncRNA sequence and structure were evaluated through supervised [classification and regression trees (CART) and support vector machines (SVM)] machine learning algorithms. In HL-1 cells, quantitative PCR of PNPase CLIP knockout mutants (KH and S1) was performed. In vitro fluorescence assays assessed PNPase RNA binding capacity and verified with PNPase CLIP. One hundred twelve (mouse) and 1,548 (human) lncRNAs were identified in the mitochondrion with Malat1 being the most abundant. Most noncoding RNAs binding PNPase were lncRNAs, including Malat1. lncRNA fragments bound to PNPase compared against randomly generated sequences of similar length showed stratification with SVM and CART algorithms. The lncRNAs bound to PNPase were used to create a criterion for binding, with experimental validation revealing increased binding affinity of RNA designed to bind PNPase compared to control RNA. The binding of lncRNAs to PNPase was decreased through the knockout of RNA binding domains KH and S1. In conclusion, sequence and secondary structural features identified by machine learning enhance the likelihood of nuclear-encoded lncRNAs binding to PNPase and undergoing import into the mitochondrion. NEW & NOTEWORTHY: Long noncoding RNAs (lncRNAs) are relatively novel RNAs with increasingly prominent roles in regulating genetic expression, mainly in the nucleus but more recently in regions such as the mitochondrion. This study explores how lncRNAs interact with polynucleotide phosphorylase (PNPase), a protein that regulates RNA import into the mitochondrion. Machine learning identified several RNA structural features that improved lncRNA binding to PNPase, which may be useful in targeting RNA therapeutics to the mitochondrion. [ABSTRACT FROM AUTHOR]

Salinity is a common abiotic stress that limits crop productivity. Although there is a wealth of evidence suggesting that miRNA and lncRNA play important roles in the response to salinity in rice seedlings and reproductive stages, the mechanism by which competing endogenous RNAs (ceRNAs) influence salt tolerance and yield in rice has been rarely reported. In this study, we conducted full whole-transcriptome sequencing of rice panicles during the reproductive period to clarify the role of ceRNAs in the salt stress response and yield. A total of 214 lncRNAs, 79 miRNAs, and 584 mRNAs were identified as differentially expressed RNAs under salt stress. Functional analysis indicates that they play important roles in GO terms such as response to stress, biosynthesis processes, abiotic stimuli, endogenous stimulus, and response to stimulus, as well as in KEGG pathways such as secondary metabolite biosynthesis, carotenoid biosynthesis, metabolic pathways, and phenylpropanoid biosynthesis. A ceRNA network comprising 95 lncRNA–miRNA–mRNA triplets was constructed. Two lncRNAs, MSTRG.51634.2 and MSTRG.48576.1, were predicted to bind to osa-miR172d-5p to regulate the expression of OsMYB2 and OsMADS63, which have been reported to affect salt tolerance and yield, respectively. Three lncRNAs, MSTRG.30876.1, MSTRG.44567.1, and MSTRG.49308.1, may bind to osa-miR5487 to further regulate the expression of a stress protein (LOC_Os07g48460) and an aquaporin protein (LOC_Os02g51110) to regulate the salt stress response. This study is helpful for understanding the underlying molecular mechanisms of ceRNA that drive the response of rice to salt stress and provide new genetic resources for salt-resistant rice breeding. [ABSTRACT FROM AUTHOR]

lncRNAs are noncoding transcripts with tissue and cancer specificity. Particularly, in breast cancer, lncRNAs exhibit subtype-specific expression; they are particularly upregulated in luminal tumors. However, no gene signature-based laboratory tests have been developed for luminal breast cancer identification or the differential diagnosis of luminal tumors, since no luminal A- or B-specific genes have been identified. Particularly, luminal B patients are of clinical interest, since they have the most variable response to neoadjuvant treatment; thus, it is necessary to develop diagnostic and predictive biomarkers for these patients to optimize treatment decision-making and improve treatment quality. In this study, we analyzed the lncRNA expression profiles of breast cancer cell lines and patient tumor samples from RNA-Seq data to identify an lncRNA signature specific for luminal phenotypes. We identified an lncRNA signature consisting of LINC01016, GATA3-AS1, MAPT-IT1, and DSCAM-AS1 that exhibits luminal subtype-specific expression; among these lncRNAs, GATA3-AS1 is associated with the presence of residual disease (Wilcoxon test, p < 0.05), which is related to neoadjuvant chemotherapy resistance in luminal B breast cancer patients. Furthermore, analysis of GATA3-AS1 expression using RNA in situ hybridization (RNA ISH) demonstrated that this lncRNA is detectable in histological slides. Similar to estrogen receptors and Ki67, both commonly detected biomarkers, GATA3-AS1 proves to be a suitable predictive biomarker for clinical application in breast cancer laboratory tests. [ABSTRACT FROM AUTHOR]

Objective To investigate the pathogenic role and underlying mechanisms of long noncoding RNAs (lncRNAs) in ANCA-associated vasculitis (AAV). Methods RNA-sequencing (RNA-seq) was applied to screen the expression profile of lncRNAs in peripheral leukocytes from five AAV patients and five healthy controls (HC). Candidate lncRNAs were preliminarily verified in peripheral leukocytes from 46 AAV patients and 35 HC by qRT-PCR. Then, the identified LINC02193 was further validated in peripheral neutrophils from 67 AAV patients, 45 HC and 64 disease controls. Correlation between LINC02193 levels and disease activity was analysed. Then, a loss-of-function study was conducted to investigate the role of LINC02193 in neutrophils activation. Furthermore, bioinformatics analysis, dual luciferase reporter and RNA immunoprecipitation assays were performed to explore the mechanism of LINC02193 regulating neutrophils activation. Results A total of 467 upregulated and 412 downregulated lncRNAs were identified in AAV patients. From the top five upregulated lncRNAs, an elevation of LINC02193 was validated in a larger sample of AAV patients, and positively correlated with disease activity. Knockdown of LINC02193 inhibited reactive oxygen species and nitric oxide production, neutrophil extracellular traps release and adhesion to endothelial cells of differentiated human promyelocytic leukaemia HL-60 cells, whereas overexpression of ICAM1 counteracted these effects. Mechanistic analysis demonstrated that LINC02193 acted as an miR-485-5p sponge to relieve the repressive effect of miR-485-5p on ICAM1, thus promoting ICAM1 expression. Conclusion LINC02193, a novel lncRNA identified in AAV, could function as competing endogenous RNAs for miR-485-5p to promote ICAM1 expression and neutrophils activation, suggesting its potential as a therapeutic target of AAV. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is a prominent public health issue and ranks as the third most prevalent cause of cancer-related mortality on a global scale. The role of long non-coding RNAs (lncRNAs) in cancer is not yet fully understood, particularly in relation to GC development. The objective of this study was to examine the expression levels of lncRNAs in GC tissues using a bioinformatics-based ranking approach. A bioinformatics methodology was employed to prioritize lncRNAs that are hypothesized to play a role in GC tumorigenesis. Moreover, a selection was made for experimental validation of the highest-ranked lncRNAs, which include HCG18, OIP5-AS1, FGD5-AS1, and NORAD. Additionally, quantitative real-time polymerase chain reaction (qRT-PCR) was employed to confirm the results obtained from bioinformatics analysis in a total of 35 GC samples and their corresponding adjacent non-tumoral samples. Receiver operating characteristic (ROC) curves and the corresponding area under the ROC curve (AUC) were utilized to evaluate the diagnostic efficacy of the lncRNAs. The bioinformatics analysis revealed that the lncRNA HCG18 is the highest-ranked lncRNA associated with GC. Furthermore, the expression levels of HCG18, OIP5-AS1, FGD5-AS1, and NORAD were found to be significantly elevated in GC samples when compared to adjacent non-tumoral samples. The calculated values for the AUC of HCG18, OIP5-AS1, FGD5-AS1, and NORAD were 0.80, 0.74, 0.73, and 0.71, respectively. The results of the study indicate that the lncRNAs HCG18, OIP5-AS1, FGD5-AS1, and NORAD may play a role in the development of GC. Additionally, the present study revealed that utilizing bioinformatic techniques can prove to be a highly effective strategy in identifying potential lncRNAs pertinent to the progression of GC. [ABSTRACT FROM AUTHOR]

Hypoxic microenvironments are intricately linked to malignant characteristics of glioblastoma multiforme (GBM). Long non-coding ribonucleic acids (lncRNAs) have been reported to be involved in the progression of GBM and closely associated with hypoxia. Nevertheless, the differential expression profiles as well as functional roles of lncRNAs in GBM cells under hypoxic conditions remain largely obscure. We explored the expression profiles of lncRNAs in hypoxic U87 cells as well as T98G cells using sequencing analysis. The effect of differentially expressed lncRNAs (DElncRNAs) was assessed through bioinformatic analysis. Furthermore, the expression of lncRNAs significantly dysregulated in both U87 and T98G cells was further validated using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Relevant cell functional experiments were also conducted. We used predicted RNA-binding proteins (RBPs) to construct an interaction network via the interaction prediction module. U87 and T98G cells showed dysregulation of 1115 and 597 lncRNAs, respectively. Gene Ontology (GO) analysis indicated that altered lncRNA expression was associated with nucleotide-excision repair and cell metabolism in GBM cells. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed the association between dysregulated lncRNAs and the Hippo signaling pathway under hypoxia. The dysregulation of six selected lncRNAs (ENST00000371192, uc003tnq.3, ENST00000262952, ENST00000609350, ENST00000610036, and NR_046262) was validated by qRT-PCR. Investigation of lncRNA-microRNA (miRNA)-mRNA networks centered on HIF-1α demonstrated cross-talk between the six validated lncRNAs and 16 related miRNAs. Functional experiments showed the significant inhibition of GBM cell proliferation, invasion, and migration by the knockdown of uc003tnq.3 in vitro. Additionally, uc003tnq.3 was used to construct a comprehensive RBP-transcription factor (TF)-miRNA interaction network. The expression of LncRNAs was dysregulated in GBM cells under hypoxic conditions. The identified six lncRNAs might exert important effect on the development of GBM under hypoxic microenvironment. [ABSTRACT FROM AUTHOR]

Ovarian cancer (OC) is a major gynecological malignancy with an annually increasing morbidity that poses a significant threat to the health of women worldwide. Most OC patients are diagnosed at an advanced stage. It is an urgent task to search for biomarkers for the diagnosis and treatment of OC. The lncRNA HCP5 (HCP5) was recently identified as an oncogene in several malignant tumors. However, the function of HCP5 in OC has rarely been reported. Herein, the levels of HCP5 and PTBP1 were found to be markedly increased in malignant OC tumor tissues and OC cell lines. In HCP5-silenced SKOV-3 and HEY cells, cell viability was markedly decreased, and the apoptosis rate was significantly increased, with more cells exhibiting G0/G1 arrest and increased expression of cleaved caspase-3 and cleaved caspase-9. Furthermore, the number of migrated cells, number of invaded cells, and migration distance were notably decreased by the knockdown of HCP5 in SKOV-3 cells and HEY cells. In the xenograft model established with SKOV-3 cells, the number of lung metastases, tumor growth, and Ki67 expression in tumor tissues were markedly decreased by the knockdown of HCP5, accompanied by an increased percentage of TUNEL-positive cells. HCP5 was found to be localized in the nucleus, and the interaction between HCP5 and PTBP1 was verified by RNA pull-down and RNA immunoprecipitation assays. Furthermore, in HCP5-overexpressing OC cells, the impacts of HCP5 on cell proliferation and apoptosis were significantly attenuated by the knockdown of PTBP1. Collectively, these results indicate that HCP5 facilitates the progression of OC by interacting with the PTBP1 protein. [ABSTRACT FROM AUTHOR]

Bipolar Disorder (BPD) and Schizophrenia (SCZ) are complex psychiatric disorders with shared symptomatology and genetic risk factors. Understanding the molecular mechanisms underlying these disorders is crucial for refining diagnostic criteria and guiding targeted treatments. In this study, publicly available RNA-seq data from post-mortem samples of the basal ganglia's striatum were analyzed using an integrative computational approach to identify differentially expressed (DE) transcripts associated with SCZ and BPD. The analysis aimed to reveal both shared and distinct genes and long non-coding RNAs (lncRNAs) and to construct competitive endogenous RNA (ceRNA) networks within the striatum. Furthermore, the functional implications of these identified transcripts are explored, alongside their presence in established databases such as BipEx and SCHEMA. A significant outcome of our analysis was the identification of 21 DEmRNAs and 1 DElncRNA shared between BPD and SCZ across the Caudate, Putamen, and Nucleus Accumbens. Another noteworthy finding was the identification of Hub nodes within the ceRNA networks that were linked to major psychosis. Particularly, MED19, HNRNPC, MAGED4B, KDM5A, GOLGA7, CHASERR, hsa-miR-4778-3p, hsa-miR-4739, and hsa-miR-4685-5p emerged as potential biomarkers. These findings shed light on the common and unique molecular signatures underlying BPD and SCZ, offering significant potential for the advancement of diagnostic and therapeutic strategies tailored to these psychiatric disorders. • Common and unique coding and noncoding signatures were identified in Schizophrenia (SCZ) and Bipolar Disorder (BPD). • Competitive Endogenous RNA (ceRNA) networks were constructed to uncover potential mRNA-miRNA-lncRNA regulatory interactions. • TF-TG networks were constructed to investigate potential transcriptional regulatory mechanisms associated with BPD and SCZ. • Extensive triage was performed on the identified signatures through established databases including BipEX and SCHEMA. • The possibility of ncRNA mediated regulatory pathways connecting SCZ and BPD was explored. [ABSTRACT FROM AUTHOR]

1. Skeletal muscle is an important component of chicken carcass. In chickens, the number of muscle fibres is fixed during the embryonic period, and muscle development during the embryonic period determines the muscle development potential after hatching. 2. Beijing-You (BY) and Cornish (CN) chickens show completely different growth rates and body types, and two breeds were used in this study to explore the role of lncRNAs in muscle development during different chicken embryonic periods. A systematic analysis of lncRNAs and mRNAs were conducted in the pectoral muscle tissues of BY and CN chickens at embryonic days 11 (ED11), 13 (ED13), 15 (ED15), 17 (ED17), and 1-day-old (D1) using RNA-seq. A total of 4,104 differentially expressed transcripts (DETs) were identified among the five stages, including 2,359 lncRNAs and 1,745 mRNAs. 3. The number of DETs between the two breeds at ED17 (1,658 lncRNAs and 1,016 mRNAs) was much higher than the total number of DET at all the other stages (692 lncRNAs and 729 mRNAs), indicating that the two breeds show the largest difference in gene regulation at ED17. 4. Correlation analysis was performed for all differentially expressed lncRNAs and mRNAs during the five periods. Forty-three, cis interaction pairs of lncRNA-mRNA related to chicken muscle development were predicted. The expression of four pairs was verified, and the results showed MSTRG.12395.2-FGFBP2 and MSTRG.18590.6-FMOD were significantly up-regulated in CN at ED11 compared to BY and might be important candidate genes for embryonic muscle development. [ABSTRACT FROM AUTHOR]

For trees originating from boreal and temperate regions, the dormancy‐to‐active transition, also known as bud dormancy release and bud break, are crucial processes that allow trees to reactive growth in the spring. The molecular mechanisms underlying these two processes remain poorly understood. Here, through integrative multiomics analysis of the transcriptome, DNA methylome, and proteome, we gained insights into the reprogrammed cellular processes associated with bud dormancy release and bud break. Our findings revealed multilayer regulatory landscapes governing bud dormancy release and bud break regulation, providing a valuable reference framework for future functional studies. Based on the multiomics analysis, we have determined a novel long intergenic noncoding RNA named Phenology Responsive Intergenic lncRNA 1 (PRIR1) plays a role in the activation of bud break. that the molecular mechanism of PRIR1 has been preliminary explored, and it may partially promote bud break by activating its neighbouring gene, EXORDIUM LIKE 5 (PtEXL5), which has also been genetically confirmed as an activator for bud break. This study has revealed a lncRNA‐mediated regulatory mechanism for the control of bud break in Populus, operating independently of known regulatory pathways. Summary statement: we report the multilayer regulatory landscapes of dormancy release and bud break regulation in hybrid poplar (Populus tremula x alba). We also identify a long intergenic noncoding RNA PRIR1 and characterise its role in dormancy release. Our study provides a useful reference framework for dormancy release and bud break regulation studies. [ABSTRACT FROM AUTHOR]

Summary: Branch number is one of the most important agronomic traits of fruit trees such as peach. Little is known about how LncRNA and/or miRNA modules regulate branching through transcription factors.Here, we used molecular and genetic tools to clarify the molecular mechanisms underlying brassinosteroid (BR) altering plant branching.We found that the number of sylleptic branch and BR content in pillar peach ('Zhaoshouhong') was lower than those of standard type ('Okubo'), and exogenous BR application could significantly promote branching. PpTCP4 expressed great differentially comparing 'Zhaoshouhong' with 'Okubo'. PpTCP4 could directly bind to DWARF2 (PpD2) and inhibited its expression. PpD2 was the only one differentially expressed key gene in the path of BR biosynthesis. At the same time, PpTCP4 was identified as a target of miR6288b‐3p. LncRNA1 could act as the endogenous target mimic of miR6288b‐3p and repress expression of miR6288b‐3p. Three deletions and five SNP sites of lncRNA1 promoter were found in 'Zhaoshouhong', which was an important cause of different mRNA level of PpTCP4 and BR content. Moreover, overexpressed PpTCP4 significantly inhibited branching.A novel mechanism in which the lncRNA1‐miR6288b‐3p‐PpTCP4‐PpD2 module regulates peach branching number was proposed. [ABSTRACT FROM AUTHOR]

Marek's disease (MD) is a neoplastic disease that significantly affects the poultry industry. Long non-coding RNAs (lncRNAs) are crucial regulatory factors in various biological processes, including tumourigenesis. However, the involvement of novel lncRNAs in the course of MD virus (MDV) infection is still underexplored. Here, we present the first comprehensive characterization of differentially expressed lncRNAs in chicken spleen at different stages of MDV infection. A series of differentially expressed lncRNAs was identified at each stage of MDV infection through screening. Notably, our investigation revealed a novel lncRNA, lncRNA 803, which exhibited significant differential expression at different stages of MDV infection and was likely to be associated with the p53 pathway. Further analyses demonstrated that the overexpression of lncRNA 803 positively regulated the expression of p53 and TP53BP1 in DF-1 cells, leading to the inhibition of apoptosis. This is the first study to focus on the lncRNA expression profiles in chicken spleens during MDV pathogenesis. Our findings highlight the potential role of the p53-related novel lncRNA 803 in MD pathogenesis and provide valuable insights for decoding the molecular mechanism of MD pathogenesis involving non-coding RNA. RESEARCH HIGHLIGHTS Differentially expressed lncRNAs in spleens of chickens infected with Marek's disease virus at different stages were identified for the first time. The effects of novel lncRNA 803 on p53 pathway and apoptosis of DF-1 cells were reported for the first time. [ABSTRACT FROM AUTHOR]

Kawasaki disease (KD) and Henoch-Schönlein purpura (HSP) are the two most predominant types of childhood vasculitis. In childhood vasculitis, factors such as lack of sensitive diagnostic indicators and adverse effects of drug therapy may cause multiorgan system involvement and complications and even death. Many studies suggest that long noncoding RNAs (lncRNAs) are involved in the mechanism of vasculitis development in children and can be used to diagnose or predict prognosis by lncRNAs. In existing drug therapies, lncRNAs are also involved in drug-mediated treatment mechanisms and are expected to improve drug toxicity. The aim of this review is to summarize the link between lncRNAs and the pathogenesis of KD and HSP. In addition, we review the potential applications of lncRNAs in multiple dimensions, such as diagnosis, treatment, and prognosis prediction. This review highlights that targeting lncRNAs may be a novel therapeutic strategy to improve and treat KD and HSP. [ABSTRACT FROM AUTHOR]

Exosomes play a key role in colorectal cancer (CRC) related processes. This review explores the various functions of exosomes in CRC and their potential as diagnostic markers, therapeutic targets, and drug delivery vehicles. Exosomal long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) significantly influence CRC progression. Specific exosomal lncRNAs are linked to drug resistance and tumor growth, respectively, highlighting their therapeutic potential. Similarly, miRNAs like miR-21, miR-10b, and miR-92a-3p, carried by exosomes, contribute to chemotherapy resistance by altering signaling pathways and gene expression in CRC cells. The review also discusses exosomes' utility in CRC diagnosis. Exosomes from cancer cells have distinct molecular signatures compared to healthy cells, making them reliable biomarkers. Specific exosomal lncRNAs (e.g., CRNDE-h) and miRNAs (e.g., miR-17-92a) have shown effectiveness in early CRC detection and monitoring of treatment responses. Furthermore, exosomes show promise as vehicles for targeted drug delivery. The potential of mesenchymal stem cell (MSC)-derived exosomes in CRC treatment is also noted, with their role varying from promoting to inhibiting tumor progression. The application of multi-omics approaches to exosome research is highlighted, emphasizing the potential for discovering novel CRC biomarkers through comprehensive genomic, transcriptomic, proteomic, and metabolomic analyses. The review also explores the emerging field of exosome-based vaccines, which utilize exosomes' natural properties to elicit strong immune responses. In conclusion, exosomes represent a promising frontier in CRC research, offering new avenues for diagnosis, treatment, and prevention. Their unique properties and versatile functions underscore the need for continued investigation into their clinical applications and underlying mechanisms. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative disease with a long incubation period. While extensive research has led to the construction of long non-coding RNA (lncRNA)-associated competing endogenous RNA (ceRNA) regulatory networks, which primarily derived from differential analyses between clinical AD patients and control individuals or mice, there remains a critical knowledge gap pertaining to the dynamic alterations in transcript expression profiles that occur with age, spanning from the pre-symptomatic stage to the onset of AD. In the present study, we examined the transcriptomic changes in AD model mice at three distinct stages: the unaffected (un-) stage, the pre-onset stage, and the late-onset stage, and identified 14, 57, and 99 differentially expressed mRNAs (DEmRs) in AD model mice at 3, 6, and 12 months, respectively. Among these, we pinpointed 16 mRNAs closely associated with inflammation and immunity and excavated their lncRNA-mRNA regulatory network based on a comprehensive analysis. Notably, our preliminary analysis suggested that four lncRNAs (NONMMUT102943, ENSMUST00000160309, NONMMUT083044, and NONMMUT126468), eight miRNAs (miR-34a-5p, miR-22-5p, miR-302a/b-3p, miR-340-5p, miR-376a/b-5p, and miR-487b-5p), and four mRNAs (C1qa, Cd68, Ctss, and Slc11a1) may play pivotal roles in orchestrating immune and inflammatory responses during the early stages of AD. Our study has unveiled age-related AD risk genes, and provided an analytical framework for constructing lncRNA-mRNA networks using time series data and correlation analysis. Most notably, we have successfully constructed a comprehensive regulatory ceRNA network comprising genes intricately linked to inflammatory and immune functions in AD. [ABSTRACT FROM AUTHOR]

A previous study indicated that patients with androgenic alopecia (AGA) have significantly reduced levels of LncRNA RP11-818O24.3. This study investigates whether LncRNA RP11-818O24.3 promotes hair-follicle recovery and its possible mechanism. Hair alteration and cutaneous histopathological changes induced by testosterone propionate were observed by H&E and bromodeoxyuridinc (BrdU) stain to evaluate the therapeutic effect of LncRNA RP11-818O24.3 in C57BL/6 J mice. The cellular viability was analyzed in LncRNA RP11-818O24.3-transfected human hair-follicle stem cells (HFSCs) in vitro. The signaling pathways and pro-proliferative factors were investigated by transcriptomic gene sequencing and qRT-PCR. LncRNA RP11-818O24.3 transfection successfully recovered hair growth and hair-follicle cells in AGA mice. In a series of HFSC studies in vitro, LncRNA RP11-818O24.3 transfection greatly promoted cellular proliferation and decreased cellular apoptosis. Transcriptome gene sequencing suggested that the phosphatidylinositol 3-kinase (PI3K)-Akt pathway was upregulated by LncRNA RP11-818O24.3. The qRT-PCR results showed that fibroblast growth factor (FGF)-2 was 14-times upregulated after LncRNA RP11-818O24.3 transfection. Hair-follicle recovery activity of LncRNA RP11-818O24.3 may involve the upregulation of FGF2 and PI3K-Akt to promote follicle stem cell survival. These data not only provide a theoretical basis for AGA development but also reveal a novel therapeutic method for AGA patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

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 FROM AUTHOR]

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 FROM AUTHOR]

Malaria transmission and endemicity in Africa remains hugely disproportionate compared to the rest of the world. The complex life cycle of P. falciparum (Pf) between the vertebrate human host and the anopheline vector results in differential expression of genes within and between hosts. An in-depth understanding of Pf interaction with various human genes through regulatory elements will pave way for identification of newer tools in the arsenal for malaria control. Therefore, the regulatory elements (REs) involved in the over- or under-expression of various host immune genes hold the key to elucidating alternative control measures that can be applied for disease surveillance, prompt diagnosis and treatment. We carried out an RNAseq analysis to identify differentially expressed genes and network elucidation of non-coding RNAs and target genes associated with immune response in individuals with different clinical outcomes. Raw RNAseq datasets, retrieved for analyses include individuals with severe (Gambia—20), symptomatic (Burkina Faso—15), asymptomatic (Mali—16) malaria as well as uninfected controls (Tanzania—20; Mali—36). Of the total 107 datasets retrieved, we identified 5534 differentially expressed genes (DEGs) among disease and control groups. A peculiar pattern of DEGs was observed, with individuals presenting with severe/symptomatic malaria having the highest and most diverse upregulated genes, while a reverse phenomenon was recorded among asymptomatic and uninfected individuals. In addition, we identified 141 differentially expressed micro RNA (miRNA), of which 78 and 63 were upregulated and downregulated respectively. Interactome analysis revealed a moderate interaction between DEGs and miRNAs. Of all identified miRNA, five were unique (hsa-mir-32, hsa-mir-25, hsa-mir-221, hsa-mir-29 and hsa-mir-148) because of their connectivity to several genes, including hsa-mir-221 connected to 16 genes. Six-hundred and eight differentially expressed long non coding RNA (lncRNA) were also identified, including SLC7A11, LINC01524 among the upregulated ones. Our study provides important insight into host immune genes undergoing differential expression under different malaria conditions. It also identified unique miRNAs and lncRNAs that modify and/or regulate the expression of various immune genes. These regulatory elements we surmise, have the potential to serve a diagnostic purpose in discriminating between individuals with severe/symptomatic malaria and those with asymptomatic infection or uninfected, following further clinical validation from field isolates. [ABSTRACT FROM AUTHOR]

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 < 0.05). Furthermore, the MEG3 rs7158663 AA genotype and the A allele also indicated an increased risk of NPC (p < 0.05). The subgroup analysis of age, EBV infection, gender, nationality, smoking, and drinking status revealed no marked association between rs1859168 and rs7158663 genotypes and these potential confounding factors. Moreover, it was observed that rs1859168 CC and rs7158663 AA genotypes were related to local tumor invasion and lymph node metastasis. Additionally, HOTTIP indicated a marked elevation, while MEG3 substantially reduced in NPC samples than the normal nasopharyngeal biospecimens. Patients who carried CC or CA genotypes rather than the HOTTIP rs1859168 AA genotype, had substantially higher HOTTIP levels, while patients with rs7158663 AA or GA genotypes indicated notably lower expression of MEG3 than GG genotype carriers. Conclusion: Individuals with genetic variants of HOTTIP rs1859168 and MEG3 rs7158663 might have an increased risk of NPC susceptibility and related clinicopathologic characteristics, potentially by affecting the expression of HOTTIP and MEG3. [ABSTRACT FROM AUTHOR]

Objective: Disulfidptosis is a newly recognized form of regulated cell death that has been linked to cancer progression and prognosis. Despite this association, the prognostic significance, immunological characteristics and treatment response of disulfidptosis-related lncRNAs (DRLs) in ovarian cancer have not yet been elucidated. Methods: The lncRNA data and clinical information for ovarian cancer and normal samples were obtained from the UCSC XENA. Differential expression analysis and Pearson analysis were utilized to identify core DRLs, followed by LASSO algorithm. Random Survival Forest was used to construct a prognostic model. The relationships between risk scores, RNA methylation, immune cell infiltration, mutation, responses to immunotherapy and drug sensitivity analysis were further examined. Additionally, qRT-PCR experiments were conducted to validate the expression of the core DRLs in human ovarian cancer cells and normal ovarian cells and the scRNA-seq data of the core DRLs were obtained from the GEO dataset, available in the TISCH database. Results: A total of 8 core DRLs were obtained to construct a prognostic model for ovarian cancer, categorizing all patients into low-risk and high-risk groups using an optimal cutoff value. The AUC values for 1-year, 3-year and 5-year OS in the TCGA cohort were 0.785, 0.810 and 0.863 respectively, proving a strong predictive capability of the model. The model revealed the high-risk group patients exhibited lower overall survival rates, higher TIDE scores and lower TMB levels compared to the low-risk group. Variations in immune cell infiltration and responses to therapeutic drugs were observed between the high-risk and low-risk groups. Besides, our study verified the correlations between the DRLs and RNA methylation. Additionally, qRT-PCR experiments and single-cell RNA sequencing data analysis were conducted to confirm the significance of the core DRLs at both cellular and scRNA-seq levels. Conclusion: We constructed a reliable and novel prognostic model with a DRLs cluster for ovarian cancer, providing a foundation for further researches in the management of this disease. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Many studies have shown that long non-coding RNAs (lncRNAs) play key regulatory roles in various biological processes. However, the importance and molecular regulatory mechanisms of lncRNAs in donkey intramuscular fat deposition remain to be further investigated. In this study, we used published transcriptomic data from the longissimus dorsi muscle of Guangling donkeys to identify lncRNAs and obtained 196 novel lncRNAs. Compared with the coding genes, the novel lncRNAs and the known lncRNAs exhibited some typical features, such as shorter transcript length and smaller exons. A total of 272 coding genes and 52 lncRNAs were differentially expressed between the longissimus dorsi muscles of the low-fat and high-fat groups. The differentially expressed genes were found to be involved in various biological processes related to lipid metabolism. The potential target genes of differentially expressed lncRNAs were predicted by cis and trans. Functional analysis of lncRNA targets showed that some lncRNAs may act on potential target genes involved in lipid metabolism processes and regulate lipid deposition in the longissimus dorsi muscle. This study provides valuable information for further investigation of the molecular mechanisms of lipid deposition traits in donkeys, which may improve meat traits and facilitate the selection process of donkeys in future breeding. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is one of the most common digestive tract malignant tumors in the world. At the time of initial diagnosis, it frequently presents with local or distant metastasis, contributing to poor prognosis in patients. Neutrophil extracellular traps (NETs) constitute a mechanism employed by neutrophils that is intricately associated with tumor progression, prognosis, and response to immunotherapy and chemotherapy. Despite this, the specific involvement of NETs-related long non-coding RNAs (lncRNAs) in gastric cancer remains unclear. A prognostic model for NETs-related lncRNAs was constructed through correlation analysis, COX regression analysis, and least absolute shrinkage and selection operator regression (LASSO) analysis. The predictive performance of the model was assessed using Kaplan–Meier survival curves, receiver operating characteristic (ROC) curves, facilitating the exploration of the relationship between disease onset and prognosis in gastric cancer. Additionally, differences in the tumor microenvironment and response to immunotherapy among gastric cancer patients across high- and low-risk groups were analyzed. Furthermore, a prognostic nomogram integrating the risk score with relevant clinicopathological parameters was developed. The prognostic prediction model for gastric cancer, derived from NETs-related lncRNAs in this study, demonstrates robust prognostic capabilities, serving as a valuable adjunct to traditional tumor staging. This model holds promise in offering novel guidelines for the precise treatment of gastric cancer, thereby potentially improving patient outcomes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

CRC poses a significant challenge in the global health domain, with a high number of deaths attributed to this disease annually. If CRC is detected only in its advanced stages, the difficulty of treatment increases significantly. Therefore, biomarkers for the early detection of CRC play a crucial role in improving patient outcomes and increasing survival rates. The development of a reliable biomarker for early detection of CRC is particularly important for timely diagnosis and treatment. However, current methods for CRC detection, such as endoscopic examination, blood, and stool tests, have certain limitations and often only detect cases in the late stages. To overcome these constraints, researchers have turned their attention to molecular biomarkers, which are considered a promising approach to improving CRC detection. Non-invasive methods using biomarkers such as mRNA, circulating cell-free DNA, microRNA, LncRNA, and proteins can provide more reliable diagnostic information. These biomarkers can be found in blood, tissue, stool, and volatile organic compounds. Identifying molecular biomarkers with high sensitivity and specificity for the early and safe, economic, and easily measurable detection of CRC remains a significant challenge for researchers. [ABSTRACT FROM AUTHOR]

This document provides a list of scientific articles related to gene regulation, infertility, and reproductive health. The articles cover various topics, including the role of long non-coding RNAs in biological processes, the impact of genetic mutations on fertility, and the effects of environmental factors on reproductive function. These references can be helpful for library patrons conducting research in these areas. [Extracted from the article]

The intramuscular fat content was closely related to the water content, tenderness, and flavor of meat, and was one of the key factors affecting meat quality. In recent years, with the continuous up‐ date and development of gene sequencing technology, genes regulating intramuscular fat deposition have been continuously explored, but the molecular mechanisms by which they play a role still need to be further improved. Therefore, this article mainly reviews the non-coding RNA and candidate genes that affect intramuscular fat deposition, in order to provide some reference for improving intramuscular fat deposition in livestock production. [ABSTRACT FROM AUTHOR]

CRNDE is an oncogene expressed as a long non-coding RNA. However, our team previously reported that the CRNDE gene also encodes a micropeptide, CRNDEP. The amino acid sequence of CRNDEP has recently been revealed by other researchers, too. This study aimed to investigate genetic alterations within the CRNDEP-coding region of the CRNDE gene, methylation profiling of this gene, and CRNDEP expression analysis. All investigations were performed on clinical material from patients with ovarian tumors of diverse aggressiveness. We found that CRNDEP levels were significantly elevated in highly aggressive tumors compared to benign neoplasms. Consistently, a high level of this micropeptide was a negative, independent, prognostic, and predictive factor in high-grade ovarian cancer (hgOvCa) patients. The cancer-promoting role of CRNDE(P), shown in our recent study, was also supported by genetic and epigenetic results obtained herein, revealing no CRNDEP-disrupting mutations in any clinical sample. Moreover, in borderline ovarian tumors (BOTS), but not in ovarian cancers, the presence of a single nucleotide polymorphism in CRNDE, rs115515594, significantly increased the risk of recurrence. Consistently, in BOTS only, the same genetic variant was highly overrepresented compared to healthy individuals. We also discovered that hypomethylation of CRNDE is associated with increased aggressiveness of ovarian tumors. Accordingly, hypomethylation of this gene's promoter/first exon correlated with hgOvCa resistance to chemotherapy, but only in specimens with accumulation of the TP53 tumor suppressor protein. Taken together, these results contribute to a better understanding of the role of CRNDE(P) in tumorigenesis and potentially may lead to improvements in screening, diagnosis, and treatment of ovarian neoplasms. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigates the role of non-coding RNAs in resistance to the antiandrogen drug darolutamide in prostate cancer. RNA sequencing identified LOC730101 as a significantly elevated lncRNA in darolutamide-resistant cancer cells. Silencing LOC730101 reduced cancer cell proliferation, in support of its role in drug-resistant cancer growth. Elevated LOC730101 levels were observed in metastatic castration-resistant prostate cancer (CRPC) tumors compared to primary prostate tumors. LOC730101 modulates the expression of cell cycle genes by suppressing microRNA miR-1-3p. Hi-C sequencing revealed that the LOC730101 gene is situated within a dynamic topologically associating domain (TAD) that is activated in resistant cells. This study indicates that LOC730101 is crucial for darolutamide resistance and a potential target to overcome antiandrogen resistance in CRPC. Antiandrogen is part of the standard-of-care treatment option for metastatic prostate cancer. However, prostate cancers frequently relapse, and the underlying resistance mechanism remains incompletely understood. This study seeks to investigate whether long non-coding RNAs (lncRNAs) contribute to the resistance against the latest antiandrogen drug, darolutamide. Our RNA sequencing analysis revealed significant overexpression of LOC730101 in darolutamide-resistant cancer cells compared to the parental cells. Elevated LOC730101 levels were also observed in clinical samples of metastatic castration-resistant prostate cancer (CRPC) compared to primary prostate cancer samples. Silencing LOC730101 with siRNA significantly impaired the growth of darolutamide-resistant cells. Additional RNA sequencing analysis identified a set of genes regulated by LOC730101, including key players in the cell cycle regulatory pathway. We further demonstrated that LOC730101 promotes darolutamide resistance by competitively inhibiting microRNA miR-1-3p. Moreover, by Hi-C sequencing, we found that LOC730101 is located in a topologically associating domain (TAD) that undergoes specific gene induction in darolutamide-resistant cells. Collectively, our study demonstrates the crucial role of the lncRNA LOC730101 in darolutamide resistance and its potential as a target for overcoming antiandrogen resistance in CRPC. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Certain long non-coding RNAs (lncRNAs) have potential peptide-coding abilities. Here, the role and molecular basis of the RNF217-AS1-encoded peptide in stomach cancer (SC) tumorigenesis were explored. Here, lncRNAs associated with SC pathogenesis and macrophage infiltration and lncRNAs with peptide-coding potential were searched by bioinformatics analysis. The gene mRNA and protein levels were examined by RT-qPCR and western blot assays, respectively. Cell viability, migratory, and invasive abilities were measured by CCK-8, Transwell migration, and Transwell invasion assays, respectively. The potential biological processes related to lncRNA RNF217-AS1 were identified by single-gene GSEA analysis. The effect of RNF217-AS1-encoded peptide on SC tumorigenesis was examined by mouse xenograft experiments. The results showed that lncRNA NR2F1-AS1 and RNF217-AS1 were differentially expressed and associated with macrophage infiltration in SC, and they had the ability to translate into short peptides. The RNF217-AS1 ORF-encoded peptide could reduce SC cell viability, inhibit cell migration and invasion, as well as hinder the development of SC xenograft tumors. The RNF217-AS1 ORF-encoded peptide in human SC AGS cells suppressed THP-1 cell migration, triggered the differential expression of CXCL1/CXCL2/CXCL8/CXCL12, and inactivated the TLR4/NF-κB/STAT1 signaling pathways. As a conclusion, the RNF217-AS1 ORF-encoded peptide hindered SC progression in vitro and in vivo and suppressed macrophage recruitment and pro-inflammatory responses in SC. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]