MicroRNA let-7g cooperates with interferon/ribavirin to repress hepatitis C virus replication

J Mol Med (Berl). 2016 Mar;94(3):311-20. doi: 10.1007/s00109-015-1348-1. Epub 2015 Oct 21.

Abstract

MicroRNAs (miRNA) have been implicated in HCV infection. The present study analyzed the effects of let-7g on HCV infection in vitro, in clinical tissue and serum samples. Here, we show that the expression of let-7g in serum and liver tissue is significantly higher in patients with sustained virologic response (SVR). We show that interferon (IFN)/ribavirin (RBV) induces let-7g expression through p38/AP-1 signaling. Overexpression of let-7g reduced HCV gene or core protein level and inhibited the HCV viral load. The let-7g and IFN/RBV have additively inhibitory effect on HCV replication. These data implicate let-7g as a new therapeutic drug to additively cooperate with IFN/RBV to repress HCV replication. Key messages: let-7g expression is increased in serum and liver tissue of patients with SVR. Interferon/ribavirin induces let-7g expression through p38/AP-1 signaling. Overexpression of let-7g can repress HCV replication. Let-7g additively cooperates with interferon/ribavirin to repress HCV replication. Lin28B silencing can reverse let-7g expression and repress HCV replication.

Keywords: HCV; IFN; JFH; Let-7g; RBV.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology*
  • Antiviral Agents / therapeutic use
  • Cell Line
  • Hepacivirus / drug effects*
  • Hepacivirus / genetics
  • Hepacivirus / physiology
  • Hepatitis C / blood
  • Hepatitis C / drug therapy*
  • Hepatitis C / genetics*
  • Hepatitis C / virology
  • Humans
  • Interferon-alpha / pharmacology*
  • Interferon-alpha / therapeutic use
  • Liver / metabolism
  • Liver / pathology
  • Liver / virology
  • MAP Kinase Signaling System / drug effects
  • MicroRNAs / blood
  • MicroRNAs / genetics*
  • Ribavirin / pharmacology*
  • Ribavirin / therapeutic use
  • Up-Regulation / drug effects
  • Viral Load / drug effects
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Interferon-alpha
  • MicroRNAs
  • mirnlet7 microRNA, human
  • Ribavirin