Clinical significance and potential of hepatic microRNA-122 expression in hepatitis C

Liver Int. 2011 Apr;31(4):474-84. doi: 10.1111/j.1478-3231.2010.02433.x. Epub 2010 Dec 30.

Abstract

Background and aims: MicroRNAs are small non-coding RNA molecules that post-transcriptionally regulate gene expression. Liver-specific microRNA-122 (miR-122) has been shown to facilitate the replication of hepatitis C virus (HCV) in human hepatoma cells in vitro. However, the clinical significance of hepatic miR-122 on HCV in human body is unclear.

Methods: Hepatic miR-122 expression was quantified using quantitative reverse-transcription polymerase chain reaction. We investigated the correlation between miR-122 expression and HCV load in liver samples from 185 patients seropositive for HCV antibody, including 151 patients seropositive for HCV RNA, and 31 patients seronegative for HCV RNA.

Results: Although hepatic miR-122 expression was weakly and positively correlated with the serum HCV load (ρ=0.19, P<0.05), it was not correlated with the hepatic HCV load (ρ=-0.14, P=0.08). The absence of a correlation between miR-122 expression and hepatic HCV load was also confirmed after stratification of histopathological liver damage (inflammatory activity grades and fibrosis stages). Furthermore, hepatic miR-122 expression in patients seronegative for HCV RNA was significantly higher than that in patients seropositive for HCV RNA (P<0.0001). The level of hepatic miR-122 expression was inversely correlated with the severity of functional and histopathological liver damage (P<0.0001), serum transaminase levels (P<0.0005).

Conclusions: Compared with in vitro findings, hepatic miR-122 expression is not correlated with HCV load in the human liver. Therefore, miR-122, by itself, is not a critical molecular target for HCV therapy. MiR-122 expression is inversely correlated with both functional and histopathological liver damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Female
  • Hepatitis Antibodies / blood
  • Hepatitis C / genetics
  • Hepatitis C / metabolism*
  • Humans
  • Japan
  • Liver / metabolism*
  • Liver / pathology
  • Male
  • MicroRNAs / metabolism*
  • Middle Aged
  • RNA, Viral / blood
  • Reverse Transcriptase Polymerase Chain Reaction
  • Statistics, Nonparametric
  • Viral Load

Substances

  • Hepatitis Antibodies
  • MIRN122 microRNA, human
  • MicroRNAs
  • RNA, Viral