Identification of potential miRNA–mRNA regulatory network contributing to pathogenesis of HBV-related HCC

Abstract

BackgroundHepatitis B virus (HBV) is one of the major risk factors of hepatocellular carcinoma (HCC). Increasing evidence indicates that microRNA (miRNA)–mRNA axis is involved in HCC. However, a comprehensive miRNA–mRNA regulatory network in HBV-related HCC is still absent. This study aims to identify potential miRNA–mRNA regulatory pathways contributing to pathogenesis of HBV-related HCC.MethodsMicroarray GSE69580 was downloaded from Gene Expression Omnibus (GEO) database. GEO2R and ‘R-limma’ were used to conduct differential expression analysis. The common miRNAs appeared in the two analytic sets were screened as potential differentially expressed miRNAs (DE-miRNAs). The prognostic roles of screened DE-miRNAs in HCC were further evaluated using Kaplan–Meier plotter database. Target genes of DE-miRNAs were predicted by miRNet. Then, protein–protein interaction (PPI) networks were established for these targets via the STRING database, after which hub genes in the networks were identified by Cytoscape. Functional annotation and pathway enrichment analyses for the target genes were performed through DAVID database. Three enriched pathways related to HBV-related HCC were selected for further analysis and potential target genes commonly appeared in all three pathways were screened. Cytoscape was employed to construct miRNA-hub gene network. The expression and correlation of potential miRNAs and targets were further detected in clinical HBV-related HCC samples by qRT-PCR.Results7 upregulated and 9 downregulated DE-miRNAs were accessed. 5 of 7 upregulated DE-miRNAs and 5 of 7 downregulated DE-miRNAs indicated significant prognostic roles in HCC. 2312 and 1175 target genes were predicted for the upregulated and downregulated DE-miRNAs, respectively. TP53 was identified as the hub gene in the PPI networks. Pathway enrichment analysis suggested that these predicted targets were linked to hepatitis B, pathways in cancer, microRNAs in cancer and viral carcinogenesis. Further analysis of these pathways screened 20 and 16 target genes for upregulated and downregulated DE-miRNAs, respectively. By detecting the expression of 36 target genes, six candidate target genes were identified. Finally, a potential miRNA–mRNA regulatory network was established based on the results of qRT-PCR and expression correlation analysis.ConclusionsIn the study, potential miRNA–mRNA regulatory pathways were identified, exploring the underlying pathogenesis and effective therapy strategy of HBV-related HCC.Electronic supplementary materialThe online version of this article (10.1186/s12967-018-1761-7) contains supplementary material, which is available to authorized users.

A Key mRNA-miRNA-lncRNA Competing Endogenous RNA Triple Sub-network Linked to Diagnosis and Prognosis of Hepatocellular Carcinoma

“…According to median expression value, all cases were classified into a low expression group and a high expression group. Subsequently, Kaplan-Meier survival plots were generated, and statistical indices containing hazard ratio (HR), 95% confidence interval (CI), RNA extraction, reverse transcription PCR and quantitative real-time fluorescence PCR were conducted as previously described (24,25). Total RNA was first extracted from cells and clinical samples using RNAiso plus Reagent (TaKaRa, Kusatsu, Japan), after which total RNA was reversely transcribed into complementary DNA (cDNA) by the PrimeScript TM RT Reagent Kit (TaKaRa, RR037A).…”

Identification of Novel SARS-CoV-2 Drug Targets by Host MicroRNAs and Transcription Factors Co-regulatory Interaction Network Analysis

“…MicroRNAs (miRNAs) are ∼19- to 24-nt non-coding RNAs that regulate gene expression by binding to target messenger RNAs (mRNAs). Several miRNAs play a key role in cell differentiation, development, pathogenesis, cellular growth, apoptosis, and disease progression ( Lou et al, 2019 ). During viral infections, host miRNAs are involved in various signaling pathways modulating host–virus interactions.…”

Retracted Article: MicroRNA-1271 modulates hepatitis B virus replication, cell proliferation and apoptosis in hepatitis B virus-related hepatocellular carcinoma by targeting SIRT1

“…5,6 Recently studies have proved that miRNAs regulate the progression of HBV-related HCC. 7,8 For instance, miR-125a-5p level is reduced in HBV-related HCC tissues, and overexpression of miR-125a-5p impedes HBV-related HCC cells growth. 9 MiRNA-520a inhibits HBV replication in HBV-related HCC cells by passivating AKT.…”