Regulation of gene expression in the development of colitis-associated colon cancer in mice fed a high-fat diet.

Studies have shown that the higher prevalence of colorectal cancers among patients with inflammatory bowel disease. Thus, proinflammatory stimulus due to a high-fat diet may impose a higher risk on the development of colorectal cancer. In the present study, we applied a transcriptomic approach to characterize the molecular mechanism(s) by which high-fat feeding aggravates colitis-associated colorectal cancer (CAC). A high-fat diet was supplied in an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced mouse model for 10 weeks and then the severity of CAC and global gene expression in colon were assessed. Although consumption of high-fat diet did not significantly aggravate CAC, it substantially changed gene expression profile in colon. In AOM/DSS treated mice (AD group) and AD mice fed a high-fat diet (AD + HF group), 34 and 54 DEGs were enriched in 'pathways in cancer', respectively. Notably, high-fat diet upregulated the expression of genes associated with spliceosome and ribosome biogenesis, and downregulated the expression of genes associated with lipid catabolism in mice treated with AOM/DSS. In addition, we identified that DEGs between the AD and AD + HF groups, were enriched in 'metabolic pathways', especially amino acid and nucleotide metabolism. Taken together, this study provides the molecular mechanism in understanding the high-fat diet-mediated CAC development.