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

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.