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.