Hepatitis C Virus Infection Induced Liver Tumors in a Humanized Mouse Model Open Access
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Hepatitis C Virus is a major cause for liver fibrosis, cirrhosis and hepatocellular carcinoma. Around 300 million people worldwide are infected with HCV. A narrow host range of HCV infection has hampered the availability of small animal model, to study the development of novel therapy. The MUP-uPA mice are crossed with SICD/bg mice to obtain triply homozygous mice expressing urokinase plasminogen activator gene under the control of mouse urinary promoter. These immunodeficient mice survive on xenografted human hepatocytes as their hepatocyte cells dead early in the life. After engraftment of fresh or frozen human hepatocytes, these mice can be infected with most HCV genotypes and develop liver tumors within six weeks post infection. Earlier research has shown that PTEN tumor suppressor is down regulated in diverse types of tumors. Also, c-MYC protooncogene is commonly increased as a tumor marker in most tumors. We observed that PTEN is decreased and c-MYC is up regulated in humanized mouse model of HCV infection induced tumors. However, Caspase 3, an important effector in apoptosis, is hardly changed. We also detected the expression levels of miRNAs (that were reported as liver cancer markers in other studies) to further confirm the HCV infection induced tumors in MUP-uPA mice. The results show that miRNA-221, 21 and 141 are induced and miRNA-122, 181 23a and 26a are markedly reduced in HCV infected liver tumors.