MiR-221 accentuates IFN׳s anti-HCV effect by downregulating SOCS1 and SOCS3

Virology. 2014 Aug:462-463:343-50. doi: 10.1016/j.virol.2014.06.024. Epub 2014 Jul 12.

Abstract

MiR-221 was reported to be upregulated and play roles in tumorigenesis of hepatitis C virus (HCV) associated hepatocellular carcinoma (HCC). However, the role of miR-221 in HCV infection remains unknown. In this study, it was found that miR-221 was upregulated in serum of HCV chronic hepatitis patients and Huh7.5.1 cells infected with HCVcc. Further studies indicated that miR-221 mimic could accentuate anti-HCV effect of IFN-α in HCVcc model, miR-221 mimic could further repressed 10% HCV RNA expression and 35-42% HCV core or NS5A protein expression in HCVcc infected Huh7.5.1 cells treated with 100IU/mL IFN-α, and miR-221 inhibitor resulted in the reverse effects. Furthermore, two members of suppressor of cytokine signaling (SOCS) family, SOCS1 and SOCS3, which are well established inhibitory factors on IFN/JAK/STAT pathway, were identified as the targets of miR-221 and were involved in the effect of miR-221. In conclusion, miR-221 could accentuate IFN׳s anti-HCV effect by targeting SOCS1 and SOCS3.

Keywords: HCV; IFN-α; Mir-221; SOCS1; SOCS3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cell Line
  • Down-Regulation
  • Female
  • Hepacivirus / immunology*
  • Hepatitis C, Chronic / immunology
  • Humans
  • Interferon-alpha / biosynthesis
  • Interferon-alpha / immunology*
  • Male
  • MicroRNAs / blood
  • MicroRNAs / metabolism*
  • Middle Aged
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins / biosynthesis*

Substances

  • Interferon-alpha
  • MIRN221 microRNA, human
  • MicroRNAs
  • SOCS1 protein, human
  • SOCS3 protein, human
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins