Studying the significance of MUC13 in hepatocellular carcinoma development
Introduction
Hepatocellular carcinoma (HCC) is considered to be an environmental disease owing to the presence of chemical carcinogens and viral components in its multistage development. Obesity and non-alcoholic fatty liver disease, which may progress to hepatocellular carcinoma (HCC), have been linked to current diets heavy in fat and charcoal-grilled processed meat, although the specific mechanisms by which nutrition contributes to hepato-carcinogenesis remain unknown. Diethylnitrosamine (DEN), a subtype of the N-nitrosocompounds found in food additives/preservatives, cigarette smoke, and pharmaceutical items, upregulates the Mucin 13 transmembrane mucin through miR-145 suppression and hepatocarcinogenesis events.
Methods
The effects of DEN treatment on Mucin 13 on hepatocellular carcinoma (HepG2, Hep3B,C3A, and SK-HEP-1) cell lines were evaluated by quantitative polymerase chain reaction. Mucin 13 expression was subsequently investigated using a chemically induced (DEN; 200 mg/kg bw; 2-AAF (150 mg/kg bw) animal model. Span diagnostics kits were used to determine the AST, ALT, and ALP activity in the serum. Sections of tumor tissue were stained with immunohistochemistry for Mucin 13 expression, and in situ hybridization was utilized to assess miR-145 levels. Molecular docking research was conducted using the Auto dock 4 package.
Results
The liver tissues of the DEN+2-AAF-administered group revealed vacuolization of hepatocytes in the centrifugal region, as well as change in the size of the nuclei. There was evident nuclear atypia in the adenoma. The serum activity of AST, ALP, and ALT correlate with the advancement of liver cancer in sick mice. In addition, DEN therapy increased the expression of Mucin 13 in liver tissues. Intriguingly, nuclear Mucin 13 staining was relatively low in normal liver tissues, but considerably elevated in DEN+2-AAF-induced HCC. These findings suggest that the nuclear localization of Mucin 13 may play a role in the malignant transformation of hepatocytes during carcinogenesis. This demonstrated a substantial downregulation of tumor suppressor miR-145 in tumor tissues relative to those of normalcontrol. Analysis of molecular models demonstrated that DEN interacts with Mucin 13 and creates a stable complex by providing several contacts with Mucin 13 residues. Furthermore, our research indicated that DEN treatment promotes the Mucin 13 and related effector proteins in liver cancer cell lines compared to vehicle controls.
Conclusion
We conclude that DEN affects Mucin 13 and related effector proteins during hepatocarcinogenesis.