Dataset Information

Construction of lncRNA-mediated ceRNA network to reveal clinically relevant lncRNA biomarkers in glioblastomas.

ABSTRACT: Cross-talk between competing endogenous RNAs (ceRNAs) play key roles in tumor development. In this study, we performed exon-level expression profiling on 26 glioblastomas (GBMs) and 6 controls to identify long non-coding RNAs (lncRNAs) of GBM initiation and progression using lncRNA-mediated ceRNA network (LMCN). The mRNA and lncRNA expression data, as well as miRNA-target interactions were firstly collected. Then, we used hypergeometric test to detect the lncRNA-mRNA interactions, followed by the construction of LMCN based on Pearson correlation coefficient. With the goal of investigation of the network organization, degree distribution of LMCN was performed. Next, the synergistic, competing lncRNA modules were identified using jActiveModule plug-in of Cytoscape. Moreover, we implemented the pathway analysis for its mRNAs in the module to explore the functions of significant lncRNAs. Using the criteria of degrees >50, 8 hub genes were identified, including EPB41L4A-AS1, ZRANB2-AS2, XIST, HOTAIR, TRAF3IP2-AS1, TPT1-AS1, PVT1 and DLG1-AS1. Furthermore, 1 synergistic, competitive module was identified. In this module, lncRNAs XIST and PVT1 were also the hubs in the synergistic, competing lncRNA module. Functional annotation demonstrated that 5 pathways were identified, including cytokine-cytokine receptor interaction, neuroactive ligand-receptor interaction, and mTOR signaling pathway. We have successfully identified several hubs (such as XIST and PVT1) and significant pathways (for instance, cytokine-cytokine receptor interaction, and neuroactive ligand-receptor interactions) for GBM via establishing the LMCN. These findings might offer potential biomarkers to early diagnose, and predict GBM prognosis in the future.

SUBMITTER: Zan XY

PROVIDER: S-EPMC6444437 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Construction of lncRNA-mediated ceRNA network to reveal clinically relevant lncRNA biomarkers in glioblastomas.

Zan Xiang-Yang XY Li Luo L

Oncology letters 20190305 5

Cross-talk between competing endogenous RNAs (ceRNAs) play key roles in tumor development. In this study, we performed exon-level expression profiling on 26 glioblastomas (GBMs) and 6 controls to identify long non-coding RNAs (lncRNAs) of GBM initiation and progression using lncRNA-mediated ceRNA network (LMCN). The mRNA and lncRNA expression data, as well as miRNA-target interactions were firstly collected. Then, we used hypergeometric test to detect the lncRNA-mRNA interactions, followed by th ...[more]

PMID: 30944630

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Project description:BackgroundAortic dissection (AD) is a rare and lethal disorder with its genetic basis remains largely unknown. Many studies have confirmed that circRNAs play important roles in various physiological and pathological processes. However, the roles of circRNAs in AD are still unclear and need further investigation. The present study aimed to elucidate the underlying molecular mechanisms of circRNAs regulation in AD based on the circRNA-associated competing endogenous RNA (ceRNA) network.MethodsExpression profiles of circRNAs (GSE97745), miRNAs (GSE92427), and mRNAs (GSE52093) were downloaded from Gene Expression Omnibus (GEO) databases, and the differentially expressed RNAs (DERNAs) were subsequently identified by bioinformatics analysis. CircRNA-miRNA-mRNA ceRNA network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to predict the potential functions of circRNA-associated ceRNA network. RNA was isolated from human arterial blood samples after which qRT-PCR was performed to confirm the DERNAs.ResultsWe identified 14 (5 up-regulated and 9 down-regulated) differentially expressed circRNAs (DEcircRNAs), 17 (8 up-regulated and 9 down-regulated) differentially expressed miRNAs (DEmiRNAs) and 527 (297 up-regulated and 230 down-regulated) differentially expressed mRNAs (DEmRNAs) (adjusted P-value <0.05 and | log2FC | > 1.0). KEGG pathway analysis indicated that DEmRNAs were related to focal adhesion and extracellular matrix receptor interaction signaling pathways. Simultaneously, the present study constructed a ceRNA network based on 1 circRNAs (hsa_circRNA_082317), 1 miRNAs (hsa-miR-149-3p) and 10 mRNAs (MLEC, ENTPD7, SLC16A3, SLC7A8, TBC1D16, PAQR4, MAPK13, PIK3R2, ITGA5, SERPINA1). qRT-PCR demonstrated that hsa_circRNA_082317 and ITGA5 were significantly up-regulated, and hsa-miR-149-3p was dramatically down-regulated in AD (n = 3).ConclusionThis is the first study to demonstrate the circRNA-associated ceRNA network is altered in AD, implying that circRNAs may play important roles in regulating the onset and progression and thus may serve as potential biomarkers for the diagnosis and treatment of AD.

Project description:BackgroundPolycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in women. An lncRNA, namely, Prader-Willi region nonprotein coding RNA 2 (PWRN2), was up-regulated in the cumulus cells of patients with PCOS. However, the molecular mechanism of PWRN2 in PCOS remains largely unknown.MethodsIn this study, the expression levels of PWRN2 were tested in cumulus cells through qRT-PCR analysis to confirm its potential roles in oocyte nuclear maturation of PCOS. A PWRN2-mediated ceRNA network was constructed based on three microarray datasets to investigate the molecular mechanism of PWRN2 in oocyte development of patients with PCOS. The direct interactions of the candidate genes of the ceRNA network were also demonstrated by dual-luciferase reporter assay.ResultsPWRN2 was found to be associated with oocyte nuclear maturation in patients with PCOS in contrast to that in normal patients. Based on the microarray data, 176 lncRNAs (118 up-regulated and 58 down-regulated) and 131 mRNAs (84 up-regulated and 47 down-regulated) were identified to be regulated by PWRN2. A PWRN2-miR-92b-3p-TMEM120B ceRNA network was constructed based on results of analysis of the combined three microarray datasets (lncRNA+mRNA microarray in KGN/shPWRN2 in this study, miRNAs microarray and lncRNA+mRNA microarray in PCOS cumulus cells reported in previous studies). The coexpression characteristics of the genes (PWRN2, miR-92b-3p and TMEM120B) were detected in the cumulus cells of cumulus-oocyte complexes at different nuclear maturity stages in PCOS. These results are in accordance with the ceRNA hypothesis. Moreover, luciferase activity assay revealed that miR-92b-3p directly binds to PWRN2 and targets TMEM120B.ConclusionsPWNR2 plays important roles in oocyte nuclear maturation in PCOS by functioning as a ceRNA to reduce the availability of miR-92b-3p for TMEM120B target binding during oocyte maturation in PCOS. Our findings would provide new information and clarify abnormal oocyte development in PCOS.

Dataset Information

Construction of lncRNA-mediated ceRNA network to reveal clinically relevant lncRNA biomarkers in glioblastomas.

Publications

Construction of lncRNA-mediated ceRNA network to reveal clinically relevant lncRNA biomarkers in glioblastomas.

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