A Study on the Role of Fxyd5 for Hepatocarcinogenesis in Chemically Induced Hepatocellular Carcinoma Mouse Model

Abstract

FXYD domain-containing ion transport regulator-5 (FXYD5) indicates poor prognosis in various human cancers. In hepatocellular carcinoma (HCC), FXYD5 expression is upregulated and positively associates with enhanced cell migration and proliferation. Here, hepatocarcinogenesis was induced in wild-type and Fxyd5−/− mice by repeated carbon tetrachloride (CCl4) treatment following a diethylnitrosamine (DEN) injection to mimic human HCC phenotype, and FXYD5 involvement in HCC development was investigated. Autopsy results indicated a typical irregular macroscopic surface with fibrosis and HCC in the livers of mice treated with DEN/CCl4 as compared with normal liver tissues. Histological evaluation revealed severe liver injury in DEN/CCl4-treated group but not in control groups. A significant decrease in HCC incidence and tumor number and size was observed in Fxyd5−/− mice as compared to that in wild-type mice after DEN/CCl4 treatment. These results demonstrate the plausible role of Fxyd5 in HCC development and its function as a novel target for HCC treatment.