Posters
Presenting Author Academic/Professional Position
Mohammed Sikander
Academic Level (Author 1)
Faculty
Discipline/Specialty (Author 1)
Cancer and Immunology
Academic Level (Author 5)
Faculty
Discipline/Specialty (Author 5)
Cancer and Immunology
Discipline Track
Biomedical Science
Abstract Type
Research/Clinical
Abstract
Background: Hepatocellular carcinoma (HCC) represents a prominent contributor to cancer-related mortality globally, with its etiology closely associated with environmental factors, inclusive of chemical carcinogens and viral pathogens. Contemporary investigations have underscored the association between obesity, non-alcoholic fatty liver disease, and the Western dietary patterns characterized by elevated fats and processed meat intake. Notwithstanding these observations, the precise molecular mechanisms underpinning dietary influences on hepatocarcinogenesis remain insufficiently explored. Our study reveals that diethylnitrosamine (DEN), a N-nitroso compound commonly present in food additives and tobacco smoke, significantly upregulates MUC13 and N-Myc expression. N-Myc, a member of the Myc family of proto-oncogenes, plays a critical role in regulating gene expression, cellular growth, apoptosis, energy metabolism, and differentiation. Additionally, we examined the simultaneous expression of MUC13 and N-Myc as potential oncogenes in human HCC tumors, hypothesizing a mechanistic relationship that may be exacerbated by the downregulation of miR-145, a factor implicated in hepatocarcinogenic processes.
Methodology: A chemically induced rat model was employed using DEN and 2-acetylaminofluorene to assess the expression levels of N-Myc and MUC13. Serum biomarkers including AST, ALT, and ALP were quantified utilizing Span Diagnostics kits. N-Myc expression was evaluated in tumor tissues via immunohistochemistry, while miR-145 levels were assessed through in situ hybridization techniques. Furthermore, we examined patient-derived tissue samples to determine N-Myc and MUC13 protein expression, supported by bioinformatics analyses of publicly available datasets.
Results: Histopathological examination of liver sections from the DEN+2-AAF-treated groups revealed hepatocyte vacuolization in the centrilobular regions, along with notable nuclear size variability and pronounced nuclear atypia in adenomas. Serum concentrations of AST, ALT, and ALP exhibited a correlation with the progression of liver malignancy. DEN treatment markedly enhanced the expression of MUC13 and N-Myc in hepatic tissues, contrasting with the minimal expression observed in normal tissues. These findings indicate that the increased expression of MUC13 and N-Myc is essential to the malignant transformation of hepatocytes. A robust correlation between MUC13 and N-Myc expression was identified in human HCC specimens. Additionally, miR-145 an inhibitory regulator of MUC13 demonstrating significant downregulation in tumor tissues relative to normal controls. Molecular modeling studies indicated that DEN forms stable complexes with N-Myc through diverse interactions.
Conclusion: This study underscores the critical involvement of MUC13 and N-Myc in the progression of hepatocellular carcinoma induced by diethylnitrosamine.
Presentation Type
Poster
Recommended Citation
Sikander, Mohammed; Malik, Shabnam; Jain, Swatantra K.; Katare, Deepshikha Pande; Yallapu, Murali; and Chauhan, Subhash, "Studying molecular mechanism in the progression of hepatocellular carcinoma" (2025). Research Colloquium. 72.
https://scholarworks.utrgv.edu/colloquium/2025/posters/72
Included in
Studying molecular mechanism in the progression of hepatocellular carcinoma
Background: Hepatocellular carcinoma (HCC) represents a prominent contributor to cancer-related mortality globally, with its etiology closely associated with environmental factors, inclusive of chemical carcinogens and viral pathogens. Contemporary investigations have underscored the association between obesity, non-alcoholic fatty liver disease, and the Western dietary patterns characterized by elevated fats and processed meat intake. Notwithstanding these observations, the precise molecular mechanisms underpinning dietary influences on hepatocarcinogenesis remain insufficiently explored. Our study reveals that diethylnitrosamine (DEN), a N-nitroso compound commonly present in food additives and tobacco smoke, significantly upregulates MUC13 and N-Myc expression. N-Myc, a member of the Myc family of proto-oncogenes, plays a critical role in regulating gene expression, cellular growth, apoptosis, energy metabolism, and differentiation. Additionally, we examined the simultaneous expression of MUC13 and N-Myc as potential oncogenes in human HCC tumors, hypothesizing a mechanistic relationship that may be exacerbated by the downregulation of miR-145, a factor implicated in hepatocarcinogenic processes.
Methodology: A chemically induced rat model was employed using DEN and 2-acetylaminofluorene to assess the expression levels of N-Myc and MUC13. Serum biomarkers including AST, ALT, and ALP were quantified utilizing Span Diagnostics kits. N-Myc expression was evaluated in tumor tissues via immunohistochemistry, while miR-145 levels were assessed through in situ hybridization techniques. Furthermore, we examined patient-derived tissue samples to determine N-Myc and MUC13 protein expression, supported by bioinformatics analyses of publicly available datasets.
Results: Histopathological examination of liver sections from the DEN+2-AAF-treated groups revealed hepatocyte vacuolization in the centrilobular regions, along with notable nuclear size variability and pronounced nuclear atypia in adenomas. Serum concentrations of AST, ALT, and ALP exhibited a correlation with the progression of liver malignancy. DEN treatment markedly enhanced the expression of MUC13 and N-Myc in hepatic tissues, contrasting with the minimal expression observed in normal tissues. These findings indicate that the increased expression of MUC13 and N-Myc is essential to the malignant transformation of hepatocytes. A robust correlation between MUC13 and N-Myc expression was identified in human HCC specimens. Additionally, miR-145 an inhibitory regulator of MUC13 demonstrating significant downregulation in tumor tissues relative to normal controls. Molecular modeling studies indicated that DEN forms stable complexes with N-Myc through diverse interactions.
Conclusion: This study underscores the critical involvement of MUC13 and N-Myc in the progression of hepatocellular carcinoma induced by diethylnitrosamine.
