Dataset Information

The emerging roles of non-coding competing endogenous RNA in hepatocellular carcinoma.

ABSTRACT: Accumulating evidence has emerged revealing that noncoding RNAs (ncRNAs) play essential roles in the occurrence and development of hepatocellular carcinoma (HCC). However, the complicated regulatory interactions among various ncRNAs in the development of HCC are not entirely understood. The newly discovered mechanism of competing endogenous RNAs (ceRNAs) uncovered regulatory interactions among different varieties of RNAs. In recent years, a growing number of studies have suggested that ncRNAs, including long ncRNAs, circular RNAs and pseudogenes, play major roles in the biological functions of the ceRNA network in HCC. These ncRNAs can share microRNA response elements to affect microRNA affinity with target RNAs, thus regulating gene expression at the transcriptional level and both physiological and pathological processes. The ncRNAs that function as ceRNAs are involved in diverse biological processes in HCC cells, such as tumor cell proliferation, epithelial-mesenchymal transition, invasion, metastasis and chemoresistance. Based on these findings, ncRNAs that act as ceRNAs may be promising candidates for clinical diagnosis and treatments. In this review, we discuss the mechanisms and research methods of ceRNA networks. We also reviewed the recent advances in studying the roles of ncRNAs as ceRNAs in HCC and highlight possible directions and possibilities of ceRNAs as diagnostic biomarkers or therapeutic targets. Finally, the limitations, gaps in knowledge and opportunities for future research are also discussed.

SUBMITTER: Xu G

PROVIDER: S-EPMC7552539 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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The emerging roles of non-coding competing endogenous RNA in hepatocellular carcinoma.

Xu Gang G Xu Wei-Yu WY Xiao Yao Y Jin Bao B Du Shun-Da SD Mao Yi-Lei YL Zhang Zhong-Tao ZT

Cancer cell international 20201012

Accumulating evidence has emerged revealing that noncoding RNAs (ncRNAs) play essential roles in the occurrence and development of hepatocellular carcinoma (HCC). However, the complicated regulatory interactions among various ncRNAs in the development of HCC are not entirely understood. The newly discovered mechanism of competing endogenous RNAs (ceRNAs) uncovered regulatory interactions among different varieties of RNAs. In recent years, a growing number of studies have suggested that ncRNAs, i ...[more]

PMID: 33061848

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Project description:BackgroundThis study aimed to develop multi-RNA-based models using a competing endogenous RNA (ceRNA) regulatory network to provide survival risk prediction in head and neck squamous cell carcinoma (HNSCC).MethodsAll long non-coding RNA (lncRNA), microRNA (miRNA), and mRNA expression data and clinicopathological features related to HNSCC were derived from The Cancer Genome Atlas. Differentially expressed RNAs were calculated using R. Prognostic factors were identified using univariate Cox regression analysis. Functional analysis was performed using GO, KEGG pathways, and PPI network. Based on the results, we derived a risk signature and compared high- and low-risk subgroups using LASSO regression analysis. Survival analysis and the relationship between risk signature and clinicopathological features were performed using log-rank tests and Cox regression analysis. A ceRNA regulatory network was constructed, and prognostic lncRNAs and miRNA expression levels were validated in vitro and in vivo.ResultsA list of 207 lncRNAs, 18 miRNAs and 362 mRNAs related to overall survival was established. Five lncRNAs (HOTTIP, LINC00460, RMST, SFTA1P, and TM4SF19-AS1), one miRNA (hsa-miR-206), and one mRNA (STC2) were used to construct the ceRNA network. Three prognostic models contained 13 lncRNAs, eight miRNAs, and 17 mRNAs, which correlated with the patient status, disease-free survival (DFS), stage, grade, T stage, N stage, TP53 mutation status, angiolymphatic invasion, HPV status, and extracapsular spread. KEGG pathway analysis revealed significant enrichment of "Transcriptional misregulation in cancer" and "Neuroactive ligand-receptor interaction." In addition, HOTTIP, LINC00460, miR-206 and STC2 were validated in GTEx data, GEO microarrays and six HNSCC cell lines.ConclusionsOur findings clarify the interaction of ceRNA regulatory networks and crucial clinicopathological features. These results show that prognostic biomarkers can be identified by constructing multi-RNA-based prognostic models, which can be used for survival risk prediction in patients with HNSCC.

Project description:Schizophrenia (SCZ) is a serious psychiatric condition with a 1% lifetime risk. SCZ is one of the top ten global causes of disabilities. Despite numerous attempts to understand the function of genetic factors in SCZ development, genetic components in SCZ pathophysiology remain unknown. The competing endogenous RNA (ceRNA) network has been demonstrated to be involved in the development of many kinds of diseases. The ceRNA hypothesis states that cross-talks between coding and non-coding RNAs, including long non-coding RNAs (lncRNAs), via miRNA complementary sequences known as miRNA response elements, creates a large regulatory network across the transcriptome. In the present study, we developed a lncRNA-related ceRNA network to elucidate molecular regulatory mechanisms involved in SCZ. Microarray datasets associated with brain regions (GSE53987) and lymphoblasts (LBs) derived from peripheral blood (sample set B from GSE73129) of SCZ patients and control subjects containing information about both mRNAs and lncRNAs were downloaded from the Gene Expression Omnibus database. The GSE53987 comprised 48 brain samples taken from SCZ patients (15 HPC: hippocampus, 15 BA46: Brodmann area 46, 18 STR: striatum) and 55 brain samples taken from control subjects (18 HPC, 19 BA46, 18 STR). The sample set B of GSE73129 comprised 30 LB samples (15 patients with SCZ and 15 controls). Differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) were identified using the limma package of the R software. Using DIANA-LncBase, Human MicroRNA Disease Database (HMDD), and miRTarBase, the lncRNA- associated ceRNA network was generated. Pathway enrichment of DEmRNAs was performed using the Enrichr tool. We developed a protein-protein interaction network of DEmRNAs and identified the top five hub genes by the use of STRING and Cytoscape, respectively. Eventually, the hub genes, DElncRNAs, and predictive miRNAs were chosen to reconstruct the subceRNA networks. Our bioinformatics analysis showed that twelve key DEmRNAs, including BDNF, VEGFA, FGF2, FOS, CD44, SOX2, NRAS, SPARC, ZFP36, FGG, ELAVL1, and STARD13, participate in the ceRNA network in SCZ. We also identified DLX6-AS1, NEAT1, MINCR, LINC01094, DLGAP1-AS1, BABAM2-AS1, PAX8-AS1, ZFHX4-AS1, XIST, and MALAT1 as key DElncRNAs regulating the genes mentioned above. Furthermore, expression of 15 DEmRNAs (e.g., ADM and HLA-DRB1) and one DElncRNA (XIST) were changed in both the brain and LB, suggesting that they could be regarded as candidates for future biomarker studies. The study indicated that ceRNAs could be research candidates for investigating SCZ molecular pathways.

Project description:Gastric cancer (GC) is a common type of cancer, and identification of novel diagnostic biomarkers associated with this disease is important. The present study aimed to identify novel diagnostic biomarkers associated with the prognosis of GC, using an integrated bioinformatics approach. Differentially expressed long non-coding RNAs (lncRNAs) associated with GC were identified using Gene Expression Omnibus datasets (GSE58828, GSE72305 and GSE99416) and The Cancer Genome Atlas database. A competing endogenous RNA network that incorporated five lncRNAs [long intergenic non-protein coding RNA 501 (LINC00501), LINC00365, SOX21 antisense divergent transcript 1 (SOX21-AS1), GK intronic transcript 1 (GK-IT1) and DLEU7 antisense RNA 1 (DLEU7-AS1)], 29 microRNAs and 114 mRNAs was constructed. Gene Ontology and protein-protein interaction network analyses revealed that these lncRNAs may be involved in 'biological regulation', 'metabolic process', 'cell communication', 'developmental process', 'cell proliferation', 'reproduction' and the 'cell cycle'. The results of receiver operating characteristic curve analysis demonstrated that LINC00501 (AUC=0.819), LINC00365 (AUC=0.580), SOX21-AS1 (AUC=0.736), GK-IT1 (AUC=0.823) and DLEU7-AS1 (AUC=0.932) had the potential to become valuable diagnostic biomarkers for GC. Associations with clinicopathological characteristics demonstrated that LINC00501 expression was significantly associated with sex (P=0.015) and tumor grade (P=0.022). Furthermore, LINC00365 expression was significantly associated with lymph node metastasis (P=0.025). Gene set enrichment analysis revealed that LINC00501, LINC00365 and SOX21-AS1 were enriched in signaling pathways associated with GC. Reverse transcription-quantitative PCR analysis demonstrated that LINC00501 expression (P=0.043) was significantly upregulated in GC tissues, whereas the expression levels of LINC00365 (P=0.033) and SOX21-AS1 (P=0.037) were significantly downregulated in GC tissues. Taken together, the results of the present study suggest that LINC00501, LINC00365, SOX21-AS1, GK-IT1 and DLEU7-AS1 may be used as novel diagnostic biomarkers for GC, and may be functionally associated with GC development and progression.

Project description:Multiple sclerosis (MS) is an immune-mediated demyelinating and degenerative disease with unknown etiology. Inappropriate response of T-cells to myelin antigens has an essential role in the pathophysiology of MS. The clinical and pathophysiological complications of MS necessitate identification of potential molecular targets to understand the pathogenic events of MS. Since the functions and regulatory mechanisms of long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) in MS are yet uncertain, we conducted a bioinformatics analysis to explain the lncRNA-associated ceRNA axes to clarify molecular regulatory mechanisms involved in T-cells responses in MS. Two microarray datasets of peripheral blood T-cell from subjects with relapsing-remitting MS and matched controls containing data about miRNAs (GSE43590), mRNAs and lncRNAs (GSE43591) were downloaded from the Gene Expression Omnibus database. Differentially expressed miRNAs (DEmiRNAs), mRNAs (DEmRNAs), and lncRNAs (DElncRNAs) were identified by the limma package of the R software. Protein-protein interaction (PPI) network and module were developed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and the Molecular Complex Detection (MCODE) Cytoscape plugin, respectively. Using DIANA-LncBase and miRTarBase, the lncRNA-associated ceRNA axes was constructed. We conducted a Pearson correlation analysis and selected the positive correlations among the lncRNAs and mRNAs in the ceRNA axes. Lastly, DEmRNAs pathway enrichment was conducted by the Enrichr tool. A ceRNA regulatory relationship among Small nucleolar RNA host gene 1 (SNHG1), hsa-miR-197-3p, YOD1 deubiquitinase (YOD1) and zinc finger protein 101 (ZNF101) and downstream connected genes was identified. Pathway enrichment analysis showed that DEmRNAs were enriched in "Protein processing in endoplasmic reticulum" and "Herpes simplex virus 1 infection" pathways. To our knowledge, this would be the first report of a possible role of SNHG1/hsa-miR-197-3p/YOD1/ZNF101 axes in the pathogenesis of MS. This research remarks on the significance of ceRNAs and prepares new perceptions for discovering the molecular mechanism of MS.

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The emerging roles of non-coding competing endogenous RNA in hepatocellular carcinoma.

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The emerging roles of non-coding competing endogenous RNA in hepatocellular carcinoma.

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