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Background: Hepatocellular carcinoma (HCC) is a very common neoplasm worldwide, and competitive endogenous RNA (ceRNA) plays an important role in the development of HCC. The purpose of this study is to investigate the molecular mechanisms of ceRNAs in HCC. Methods: This study detects potential ceRNAs from HCC through whole genome analysis of lncRNA, miRNA and mRNA expression. We then performed high-throughput sequencing of tissues from five hepatitis B related HCC patients to screen ceRNAs and those screened ceRNAs expressions were verified on tissues from an independent group of six patients. Finally, the function of ceRNAs of interest was illustrated in vitro. Result: Functional and pathway analysis of The Cancer Genome Atlas revealed ceRNA networks. The high-throughput sequencing identified 985 upregulated and 1612 downregulated lncRNAs and 887 upregulated and 1116 downregulated mRNAs in HCC patients. Differentially expressed genes were parallel to cancer-associated processes, comprising 18 upregulated and 35 downregulated significantly enriched pathways including alcoholism and viral carcinogenesis. Among them, a potential ceRNA network was detected and verified in six HCC patients. CeRNAs of the lncRNA MAGI2-AS3/miR-374-5p/FOXO1 pathway were significantly dysregulated in HCC, and validation in vitro showed that FOXO1 is positively regulated by MAGI2-AS3 through the induction of miR-374a/b-5p in HCC cells. In addition, the overexpression of FOXO1 is associated with proliferation, migration, and invasion of HCC cells and increases apoptosis of HCC cells. MiR-374a/b-5p caused an opposite effect by directly suppressing FOXO1 in HCC cells. Conclusion: CeRNA networks were found in HCC and aberrantly expressed ceRNAs of lncRNA MAGI2-AS3/miR-374-5p/FOXO1 plays a crucial role in HCC, assisting in diagnosis and providing a method for treatment. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is the predominant form of liver cancer and is accompanied by a complex regulatory network. Increasing evidence suggests that an abnormal gene expression of EZH2 is associated with HCC progression. However, the molecular mechanism by which non-coding RNAs (ncRNAs) regulate EZH2 remains elusive. Methods: The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data were used to perform differential expression analysis and prognostic analysis. We used the Encyclopedia of RNA Interactomes (ENCORI) database to predict candidate miRNAs and lncRNAs that may bind to EZH2. Subsequently, the comprehensive analysis (including expression analysis, correlation analysis, and survival analysis) identified ncRNAs that contribute to EZH2 overexpression. Results: EZH2 was found to be upregulated in the majority of tumor types and associated with a poor prognosis. Hsa-miR-101-3p was identified as a target miRNA of EZH2. Additionally, SNHG6 and MALAT1 were identified as upstream lncRNAs of hsa-miR-101-3p. Meanwhile, correlation analysis revealed that EZH2 expression was significantly associated with the infiltration of several immune cell types in HCC. Conclusion: SNHG6 or MALAT1/hsa-miR-101-3p/EZH2 axis were identified as potential regulatory pathways in the progression of HCC. [ABSTRACT FROM AUTHOR]