The role of microRNAs during hepatitis C viral infection and liver regeneration

microRNAs (miRNAs) are newly discovered small RNAs that repress gene expression and are evolving as clinical predictors for diagnosis and prognosis of human disease. Persistent hepatitis C virus (HCV) infection causes chronic inflammation and can lead to fibrosis, cirrhosis and liver cancer. HCV-associated liver injury is characterized by increased hepatocyte proliferation. Studies have demonstrated interactions between HCV and miRNAs. We investigated the role of miRNAs during HCV infection. We used global expression analysis to measure the expression levels of 380 miRNAs comparing HCV infected human livers with uninfected livers. We correlated the altered miRNA expression levels with clinical patient data, such as stage of fibrosis, liver transaminases, and viral load. We identified several miRNAs that correlated with these parameters, including miR-21. miR-21 correlated with stage of fibrosis, liver transaminases, and viral load. We used the mouse carbon tetrachloride model to induce fibrosis and identified correlations with miR-21 expression and stage of fibrosis. Furthermore, we identified, SMAD7, an inhibitor of fibrosis, as a novel target of miR-21 providing further evidence of miR-21’s possible involvement in fibrosis development. In our patient samples, miR-21 expression also correlated with viral load. Establishing a further connection between miR-21 and HCV, we measured miR21 expression levels in HCV replicons and infectious HCVcc tissue culture models. Altered expression of miR-21 varied depending on replicon genotype and tissue culture model preventing us from establishing a consistent relationship between miR-21 expression level and HCV infection. Interestingly, miR-21 inhibition in replicon cells resulted in decreased viral replication suggesting a possible miR-21 anti-viral effect.