Functional analysis of miR-181a and Fas involved in hepatitis B virus-related hepatocellular carcinoma pathogenesis

Exp Cell Res. 2015 Feb 15;331(2):352-61. doi: 10.1016/j.yexcr.2014.11.007. Epub 2014 Nov 20.

Abstract

The hepatitis B virus (HBV) is responsible for most of hepatocellular carcinoma (HCC). However, whether HBV plays an important role during hepatocarcinogenesis through effecting miRNAs remains unknown. Here, we reported that HBV up-regulated microRNA-181a (miR-181a) by enhancing its promoter activity. Simultaneously, we found that miR-181a inhibited apoptosis in vitro and promoted tumor cell growth in vivo. TNF receptor superfamily member 6 (Fas) was further identified as a target of miR-181a. We also found that Fas could reverse the apoptosis-inhibition effect induced by miR-181a. Moreover, HBV could inhibit cell apoptosis by down-regulating Fas expression, which could be reversed by miR-181a inhibitor. Our data demonstrated that HBV suppressed apoptosis of hepatoma cells by up-regulating miR-181a expression and down-regulating Fas expression, which may provide a new understanding of the mechanism in HBV-related HCC pathogenesis.

Keywords: Apoptosis; Fas; HBV; HCC; miR-181a.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / virology*
  • Caspase 8 / analysis
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cell Transformation, Neoplastic / genetics
  • DNA, Viral / genetics
  • Down-Regulation
  • Hep G2 Cells
  • Hepatitis B / pathology
  • Hepatitis B / virology
  • Hepatitis B virus / physiology*
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology
  • Liver Neoplasms / virology*
  • Mice
  • Mice, Nude
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • Promoter Regions, Genetic / genetics
  • Transcriptional Activation / genetics
  • Tumor Burden / genetics
  • Up-Regulation
  • fas Receptor / biosynthesis
  • fas Receptor / genetics*

Substances

  • DNA, Viral
  • FAS protein, human
  • MIrn181 microRNA, human
  • MicroRNAs
  • fas Receptor
  • Caspase 8