Epigenetic Mechanisms in Hepatitis C Virus-Associated Hepatocellular Carcinoma: A Potential New Link Between Stem Cells, Virology and Cancer

Recent studies suggest that epigenetic mechanisms are not only essential for the dynamic transcriptional regulation in embryonic and somatic stem cells, but are also actively involved in tumorigenesis: genes important for pluripotency are epigenetically regulated and aberrant epigenetic changes have been detected in virtually all human malignancies studied, including Hepatocellular Carcinoma (HCC). Infection with Hepatitis C Virus (HCV) is a major risk factor for the development of HCC. Despite the fact that HCV is a RNA virus without a DNA intermediate, recent studies demonstrate that HCV viral proteins may actively participate in epigenetic regulation of hepatic cancer stem cell phenotypes and induce HCC-specific epigenetic changes. Identification of host epigenetic alterations induced by HCV infection and epigenetic differences between hepatic cancer stem cells and the bulk non-tumorigenic cancer cells, may yield potential biomarkers for early detection, as well as therapeutic targets for HCV associated HCC.