Hepatitis C virus induced up-regulation of microRNA-27: a novel mechanism for hepatic steatosis

Hepatology. 2014 Jan;59(1):98-108. doi: 10.1002/hep.26634. Epub 2013 Nov 19.


MicroRNAs (miRNAs) are small RNAs that posttranscriptionally regulate gene expression. Their aberrant expression is commonly linked with diseased states, including hepatitis C virus (HCV) infection. Herein, we demonstrate that HCV replication induces the expression of miR-27 in cell culture and in vivo HCV infectious models. Overexpression of the HCV proteins core and NS4B independently activates miR-27 expression. Furthermore, we establish that miR-27 overexpression in hepatocytes results in larger and more abundant lipid droplets, as observed by coherent anti-Stokes Raman scattering (CARS) microscopy. This hepatic lipid droplet accumulation coincides with miR-27b's repression of peroxisome proliferator-activated receptor (PPAR)-α and angiopoietin-like protein 3 (ANGPTL3), known regulators of triglyceride homeostasis. We further demonstrate that treatment with a PPAR-α agonist, bezafibrate, is able to reverse the miR-27b-induced lipid accumulation in Huh7 cells. This miR-27b-mediated repression of PPAR-α signaling represents a novel mechanism of HCV-induced hepatic steatosis. This link was further demonstrated in vivo through the correlation between miR-27b expression levels and hepatic lipid accumulation in HCV-infected SCID-beige/Alb-uPa mice.

Conclusion: Collectively, our results highlight HCV's up-regulation of miR-27 expression as a novel mechanism contributing to the development of hepatic steatosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bezafibrate
  • Cell Line, Tumor
  • Fatty Liver / etiology*
  • Hepacivirus / physiology*
  • Hepatitis C / complications*
  • Hepatitis C / metabolism
  • Hepatitis C / virology
  • Homeostasis
  • Humans
  • Lipid Metabolism
  • Liver / metabolism
  • Mice
  • Mice, SCID
  • MicroRNAs / metabolism*
  • PPAR alpha / agonists
  • Up-Regulation


  • MIRN27 microRNA, human
  • MicroRNAs
  • Mirn27 microRNA, mouse
  • PPAR alpha
  • Bezafibrate