HCV infection is a leading cause of chronic hepatitis morbidity and a cause of liver cancer, hepatocellular carcinoma (HCC). Although the infection can be controlled with anti-viral medication, the long latency and attendant infection related changes are likely to be carcinogenic in many cases. The study focuses on activities of oncogenes including miRNAs whose activities appear to promote HCC in the HCV infected liver. This is a not insignificant research topic. This proposal involves a second year continuation of a project to develop and investigate a human/mouse chimeric model of the progression of Hepatitis C Viral (HCV) infection to hepatocellular carcinoma (HCC). The project contains two aims: 1) to determine the effects of LNA-antagomiR on oncogenic gene expression in HCV infected human hepatocytes and 2) to determine the effectiveness of LNA-antagomiR in inhibiting HCV-infection HCC in a humanized mouse model.