Dataset Information

Construction of a Competitive Endogenous RNA Network and Identification of Potential Regulatory Axis in Gastric Cancer.

ABSTRACT: Background: Increasing studies has found that long non-coding RNAs (lncRNAs) play critical roles in carcinogenesis, but the underlying mechanisms remain unclear. The aim of this study is to construct a competitive endogenous RNA (ceRNA) network and to identify potential regulatory axis in gastric cancer (GC). Methods: Differentially expressed (DE) mRNAs, miRNAs, and lncRNAs were obtained by analyzing the RNA expression profiles of stomach adenocarcinoma (STAD) retrieved from The Cancer Genome Atlas (TCGA) database. The lncRNA-miRNA-mRNA regulatory networks of GC were constructed by comprehensive bioinformatics methods including functional annotation, RNA-RNA interactomes prediction, correlation analysis, and survival analysis. The interactions and correlations among ceRNAs were validated by experiments on cancer tissues and cell lines. Results: A total of 41 lncRNAs, 9 miRNAs, and 10 mRNAs were identified and selected to establish the ceRNA regulatory network of GC. Several ceRNA regulatory axes, which consist of 18 lncRNAs, 4 miRNAs, and 6 mRNAs, were obtained from the network. A potential ADAMTS9-AS2/miR-372/CADM2 axis which perfectly conformed to the ceRNA theory was further analyzed. qRT-PCR showed that ADAMTS9-AS2 knockdown remarkably increased miR-372 expression but reduced CADM2 expression, whereas ADAMTS9-AS2 overexpression had the opposite effects. Dual luciferase reporter assay indicated that miR-372 could bound to the ADAMTS9-AS2 and the 3'UTR of CADM2. Conclusion: The constructed novel ceRNA network and the potential regulatory axes might provide a novel approach of the exploring the potential mechanisms of development in GC. The ADAMTS9-AS2/miR-372/CADM2 could act as a promising target for GC treatment.

SUBMITTER: Pan H

PROVIDER: S-EPMC6787165 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Construction of a Competitive Endogenous RNA Network and Identification of Potential Regulatory Axis in Gastric Cancer.

Pan Hongda H Guo Chunmiao C Pan Jingxin J Guo Dongwei D Song Shibo S Zhou Ye Y Xu Dazhi D

Frontiers in oncology 20191004

<b>Background:</b> Increasing studies has found that long non-coding RNAs (lncRNAs) play critical roles in carcinogenesis, but the underlying mechanisms remain unclear. The aim of this study is to construct a competitive endogenous RNA (ceRNA) network and to identify potential regulatory axis in gastric cancer (GC). <b>Methods:</b> Differentially expressed (DE) mRNAs, miRNAs, and lncRNAs were obtained by analyzing the RNA expression profiles of stomach adenocarcinoma (STAD) retrieved from The Ca ...[more]

PMID: 31637209

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Project description:BackgroundGlioblastoma is the most common primary malignant brain tumor. Because of the limited understanding of its pathogenesis, the prognosis of glioblastoma remains poor. This study was conducted to explore potential competing endogenous RNA (ceRNA) network chains and biomarkers in glioblastoma by performing integrated bioinformatics analysis.MethodsTranscriptome expression data from The Cancer Genome Atlas database and Gene Expression Omnibus were analyzed to identify differentially expressed genes between glioblastoma and normal tissues. Biological pathways potentially associated with the differentially expressed genes were explored by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis, and a protein-protein interaction network was established using the STRING database and Cytoscape. Survival analysis using Gene Expression Profiling Interactive Analysis was based on the Kaplan-Meier curve method. A ceRNA network chain was established using the intersection method to align data from four databases (miRTarBase, miRcode, TargetScan, and lncBace2.0), and expression differences and correlations were verified by quantitative reverse-transcription polymerase chain reaction analysis and by determining the Pearson correlation coefficient. Additionally, an MTS assay and the wound-healing and transwell assays were performed to evaluate the effects of complement C1s (C1S) on the viability and migration and invasion abilities of glioblastoma cells, respectively.ResultsWe detected 2842 differentially expressed (DE) mRNAs, 2577 DE long non-coding RNAs (lncRNAs), and 309 DE microRNAs (miRNAs) that were dysregulated in glioblastoma. The final ceRNA network consisted of six specific lncRNAs, four miRNAs, and four mRNAs. Among them, four DE mRNAs and one DE lncRNA were correlated with overall survival (p < 0.05). C1S was significantly correlated with overall survival (p= 0.015). In functional assays, knockdown of C1S inhibited the proliferation and invasion of glioblastoma cell lines.ConclusionsWe established four ceRNA networks that may influence the occurrence and development of glioblastoma. Among them, the MIR155HG/has-miR-129-5p/C1S axis is a potential marker and therapeutic target for glioblastoma. Knockdown of C1S inhibited the proliferation, migration, and invasion of glioblastoma cells. These findings clarify the role of the ceRNA regulatory network in glioblastoma and provide a foundation for further research.

Dataset Information

Construction of a Competitive Endogenous RNA Network and Identification of Potential Regulatory Axis in Gastric Cancer.

Publications

Construction of a Competitive Endogenous RNA Network and Identification of Potential Regulatory Axis in Gastric Cancer.

Similar Datasets

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