Comprehensive Analysis of Competitive Endogenous Rnas Network Associated With Hepatocellular Carcinoma

Background: Increasing evidences show that long non-coding RNA (lncRNA) plays the role of competitive endogenous RNAs (ceRNAs) in the development and progression of cancers. The purpose of our study was to identify potential lncRNA biomarkers that serve as a therapeutic target and prognostic biomarker in HCC. Methods: The differential expression of RNAs was examined using the edgeR package. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to predict potential functions. Survival analysis and ROC curve analysis were performed to predict ceRNA network had significant prognostic value. The biological functions of MYLK-AS1 on HCC cells were studied by RNA interference approaches in vitro. Cell proliferation, migration and invasion were detected by Cell Counting Kit-8(CCK-8) assay, wound healing and transwell assay relatively. The mechanism of competitive endogenous RNAs (ceRNAs) were predicted and verified by bioinformatic analysis, western blot analysis and luciferase assays. Results: The newly constructed ceRNA network comprised 76 HCC specific lncRNAs, 15 miRNAs, and 35 mRNAs from the database (Targetscan, miRTarBase, and miRDB). 10 differentially expressed lncRNAs and 10 differentially expressed mRNAs were significantly associated with overall survival in HCC ( P value < 0.05). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathways enrichment analysis results showed the differentially expressed mRNAs were involved primarily in the most significant cancer-related signaling pathways. ROC curve analysis demonstrated that MYLK-AS1—has-mir-424—CCNE1 ceRNA network had significant prognostic value. The expression of MYLK-AS1 was up-regulated in HCC cells and tissues. Biological function analyses indicated that down-regulation of MYLK-AS1 suppressed cell proliferation, migration and invasion . MYLK-AS1 and miR-424-5p bound directly and reversibly to each other. MYLK-AS1 could positively regulate CCNE1 expression by competitively binding to miR-424-5p. Conclusion: The current study provides novel insights into the lncRNA-related ceRNA network in HCC and the MYLK-AS1 may be a candidate biomarker for molecular diagnosis and prognosis monitoring of HCC.