Mo1951 Sensitive Quantitative CpG Methylation Testing in Random Colonic Biopsies for Risk Assessment of Coexisting Dysplasia in Ulcerative Colitis Patients

Abstract

without dysplasia, miR-193a-3p was down-regulated 1.2-fold in UCrD (p=0.7) and 1.9-fold in UCD (p=0.05). UCD samples demonstrated increased methylation compared to normal controls and UC without neoplasia. There was a linear trend with decreased expression and increased methylation across all samples. 5-AZA treatment resulted in increased pri-miR193a transcript abundance in DLD1 (2.1-fold, p= 0.002), HCT116 cells (2.2-fold, p=0.02), and LoVo cells (1.2-fold, p=0.7), without significant change in mature miR-193a-3p expression. Transfection of 20nM and 50nM of miR-193a-3p in HCT116 cells down-regulated IL17RD, but not KRAS. Discussion: The gene encoding miR-193a-3p is methylated and its expression is down-regulated in IBD-associated neoplasia, suggesting that miR-193a-3p is regulated epigenetically. We identified IL17RD, an orphan receptor that potentiates IL-17 signaling, as a novel target of miR-193a-3p. As IL-17 signaling is up-regulated in inflammation and carcinogenesis, we postulate that down-regulation of miR-193a-3p contributes to cancer development in IBD via increased IL17RD.