Abstract 1945: Differential expression of miRNA in inflammation-associated colorectal carcinogenesis assayed by microRNA profiling in Muc2 −/ − mice.

Inflammatory bowel disease is an important risk factor for the development of colorectal cancer. How the inflammatory or immunological microenvironment modulates tumor initiation and development is a challenging question. Using an appropriate animal model to accurately reproduce the progression from spontaneous chronic inflammation to tumor formation contributes to better study chronic colitis-associated carcinogenesis and its underlying molecular mechanisms. Previous studies have shown that decreased number of goblet cells and reduced Muc2 expression is commonly observed in ulcerative colitis and colorectal carcinoma. We have demonstrated that targetedly knockout of the Muc2 gene in a mouse causes spontaneous colitis in the early age and carcinogenesis in small intestine, colon and rectum in the late age. Unfortunately, the underlying mechanism is not clear, although it is known that chronic inflammation plays a crucial role in malignancy transformation. Recent studies have revealed that epigenetic changes are involved in colitis-associated cancer formation, among them, microRNA (miRNA) is more important. miRNAs are small molecular noncoding RNAs and are thought to act as post-transcriptional modulators of gene expression by base-pairing with the 3′-untranslated regions of the target mRNAs, functioning in the regulation of development, differentiation, cell proliferation, programmed cell death and fat metabolism. Using the unique Muc2 knockout mouse model of colorectal cancer (Muc2−/−), we conducted miRNA array on intestinal epithelial cells isolated from 3-month old mice (4 Muc2−/− mice and 4 Muc2+/+ mice, respectively). Microarray profiling showed that 29 miRNAs from Muc2−/− mouse intestinal epithelial cells exerted lower expression enrichment and 115 miRNAs displayed higher expression enrichment, in comparison with those in Muc2+/+ mice (fold cutoff ≥2). Interestingly, most of these miRNAs were targeting oncogenes, tumor suppressors, cytokines, autophagy, inflammation, apoptosis, proliferation and differentiation. Notably, approximately 20% of the identified miRNAs showed some degrees of correlation with carcinogenic effects. The inventory of miRNA profiles in the Muc2−/− mice provides an important step toward further elucidation of miRNA function and miRNA-related gene regulatory networks in inflammation-associated cancer formation. (This work is sponsored in part by grant fund 91229115) Citation Format: Yonghua Bao, Zhiguo Chen, Qi Shi, Wenfeng Fang, Xiuli Bi, Huali Dong, Wancai Yang, Wancai Yang. Differential expression of miRNA in inflammation-associated colorectal carcinogenesis assayed by microRNA profiling in Muc2−/− mice. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1945. doi:10.1158/1538-7445.AM2013-1945