Role Of MiR-150-targeting C-Myb In Colonic Epithelial Disruption During Dextran Sulphate Sodium-induced Murine Experimental Colitis And Human Ulcerative Colitis

Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is a group of non-specific chronic inflammatory conditions of the gastrointestinal tract with unknown complex etiology. Chronic inflammatory bowel diseases are associated with differential expression of genes involved in inflammation and tissue remodelling.We surveyed the expression profile of apoptosis-related microRNAs by real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) in a dextran sulphate sodium (DSS) murine model of colitis. We found that miR-150was strongly elevated, whereas c-Myb, a transcription factor and a target gene of miR-150, was significantly reduced in colon tissue after DSS treatment. Interestingly, elevation of miR-150and down-regulation of c-Myb were also observed in human colon with active ulcerative colitis compared to the normal colon. Supporting the observation of DSS treatment inducing colonic cell apoptosis, Bcl-2, an anti-apoptotic protein known to be regulated by c-Myb, was reduced in colon tissue of DSS-treated mice. Furthermore, forced expression of pre-miR-150in colonic epithelial HT29cells strongly elevated miR-150levels and decreased c-Myb and Bcl-2levels, thus enhancing cell apoptosis induced by serum deprivation. Together, the present study presents the first evidence that miR-150and its targeting of c-Myb may serve as a new mechanism underlying the colonic epithelial disruption in DSS-induced murine experimental colitis and in active human IBD.