High Expression of MUC13 Is Associated with Tumor Development in Chemically Induced Hepatocellular Carcinoma

Background and aim: Hepatocellular carcinoma (HCC) has a poor prognosis due to ineffective therapeutic modality and lack of early diagnostic marker. Accumulating studies have shown that elevated expression of mucin 13 as potential oncogene and predictive biomarker for various cancer. However, very little is known about its expression and function for development and progression of HCC. In the present study, for the first time, we investigated the expression of Mucin 13 in chemically induced HCC model. Materials and methods: Diethyl nitrosamine (DEN) and 2-Acetylaminofluorene (2-AAF) induced method was employed for the development of hepatocellular carcinoma in Male Wistar rats. Serum and tissues are collected at regular interval of time and routinely validated for liver cancer stages. Immunohistochemistry and in situ hybridization were performed on formalin-fixed, paraffin-embedded tissues. Results: Our results demonstrate hepatocellular adenoma as observed by histopathological analysis. Biochemical analysis showed a progressive increase in the levels of serum ALT, AST and ALP, suggesting the development and progression of hepatocellular damage. Notably, mucin 13 expression gradually elevated during consecutive stages of hepatocellular carcinoma. Interestingly, an increase in nuclear localization of mucin 13 was observed in treated group as compared to control group. In situ hybridization analysis showed that a decrease in miR-145, which is inversely related with mucin 13 expression. Moreover, DEN efficiently binds mucin 13 with high affinity and thus stabilize it as demonstrated by molecular docking analysis. Conclusion: These results suggest that mucin 13 expression is closely associated with hepatocarcinogenesis and could serve as a potential predictive candidate biomarker for HCC.