MiR-363-5p as potential prognostic marker for hepatocellular carcinoma indicated by weighted co-expression network analysis of miRNAs and mRNA

Jun Zhang,Yanyu Qi,Jia Fan,Chongming Zhou

doi:10.1186/s12876-017-0637-2

Abstract

BackgroundThis study aimed to investigate potential miRNAs and genes associated with the prognosis of hepatocellular carcinoma (HCC).MethodsWeighted co-expression network analysis was utilized to analyze the mRNA and miRNA sequencing data of HCC from TCGA (The Cancer Genome Atlas) database. Significant network modules were identified, and then functions of genes in the gene network modules and target genes of miRNAs in the miRNA network modules were explored. Additionally, correlations between network modules and prognostic factors of HCC were analyzed.ResultsIn total, 10 mRNA network modules were identified, three of which were significantly related to tumor stage, NAFLD (non-alcoholic fatty liver disease) and patient age. Four miRNA network modules were identified, of which one was associated with tumor stage. Targets of hsa-miR-363-5p were found distributed in the gene network modules, such as RGPD5, RGPD6, ZNF445 and ZNF780B. Kaplan–Meier test revealed that low expression of hsa-miR-363-5p was associated with better overall survival of HCC patients.Conclusionhsa-miR-363-5p may be a potential prognostic marker for HCC.

Highlights

This study aimed to investigate potential miRNAs and genes associated with the prognosis of hepatocellular carcinoma (HCC)
The messenger RNA (mRNA) in the dark magenta module (n = 8695) were enriched for mRNA that coded for proteins involved in alternative splicing; in the dark grey module (n = 6199), they were involved with sensory transduction; in the coral module (n = 1488), they were involved with oxidoreductase (Table 1)
Module dark magenta was found to be significantly correlated with tumor stage of HCC (r = 0.2, p = 4e-5); module antique white was related to Non-alcoholic fatty liver disease (NAFLD) (r = 0.18, p = 2e-4); and module coral was associated with age (r = 0.13, p = 0.008) (Fig. 2b)

Summary

Introduction

This study aimed to investigate potential miRNAs and genes associated with the prognosis of hepatocellular carcinoma (HCC). There are few effective treatments for advanced HCC partly because the cell- and molecular-based mechanisms that contribute to the pathogenesis of this tumor type remain unclear. A series of miRNAs have been identified as tumor suppressors in HCC. The putative tumor suppressor miR-124 regulates cell aggressiveness of HCC by targeting ROCK2 and EZH2 [8]. Overexpression of miR-101 blocks epithelial-mesenchymal transition and angiogenesis of HCC via decreasing multiple genes (e.g. COX2, EZH2 and STMN1) [10]. There are some studies identified the associations between several miRNAs and clinical outcomes of HCC patients.

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