MicroRNA-581 promotes hepatitis B virus surface antigen expression by targeting Dicer and EDEM1

Carcinogenesis. 2014 Sep;35(9):2127-33. doi: 10.1093/carcin/bgu128. Epub 2014 Jun 9.

Abstract

Hepatitis B virus surface antigen (HBsAg) is an important risk factor for hepatocellular carcinoma (HCC) and is downregulated during hepatocarcinogenesis. MicroRNAs (miRNAs) are frequently deregulated in HCC tissues. However, whether the deregulation of certain miRNAs in HCC has an impact on HBsAg expression remains unclear. We found here that microRNA-581 (miR-581), which is deregulated during hepatocarcinogenesis, promoted HBsAg expression. Additionally, miR-581 targeted Dicer and endoplasmic reticulum degradation-enhancing alpha-mannosidase-like protein 1 (EDEM1) and repressed their expression. Although Dicer cannot process HBV transcripts, Dicer knockdown led to increased HBsAg secretion, most likely due to a reduction in the levels of Dicer-processed 7SL RNA fragments. Moreover, Dicer-processed 7SL RNA fragments partially inhibited the ability of miR-581 to stimulate HBsAg expression. Furthermore, we found that forced EDEM1 expression inhibited miR-581-mediated induction of HBsAg. Finally, transfection of miR-581 into HepG2.2.15 cells promoted cell proliferation and led to upregulation of genes involved in development, cell proliferation and protein secretion. Altogether, we conclude that miR-581 promotes HBsAg expression by targeting Dicer and EDEM1. Our findings suggest that downregulation of miR-581 during hepatocarcinogenesis may lead to a reduction in HBsAg expression and impede HCC development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Binding Sites
  • DEAD-box RNA Helicases / genetics*
  • DEAD-box RNA Helicases / metabolism
  • Gene Expression Regulation, Neoplastic
  • Gene Expression Regulation, Viral
  • Hep G2 Cells
  • Hepatitis B Surface Antigens / metabolism*
  • Humans
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • MicroRNAs / genetics*
  • RNA Interference
  • Ribonuclease III / genetics*
  • Ribonuclease III / metabolism

Substances

  • 3' Untranslated Regions
  • EDEM1 protein, human
  • Hepatitis B Surface Antigens
  • MIRN581 microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • DICER1 protein, human
  • Ribonuclease III
  • DEAD-box RNA Helicases