P107 MicroRNA signatures can differentiate the inflamed colonic mucosa from non-inflamed mucosa in ulcerative colitis patients

Differential expression of miRNAs have been studied in various cancers and inflammatory diseases including inflammatory bowel disease (IBD). In many studies, it has been seen that the miRNA profile of UC patients differs significantly from the healthy subjects but still there are very few reports about the spatial expression miRNA within the inflamed and non-inflamed pockets of UC patients. In the present study, we looked at the expression profile of miRNA in the UC vs. controls as well as in the inflamed vs. non inflamed regions of UC patients. We also looked at the biological relevance of miRNA dysregulation by predicting the potential targets of these miRNA and the signalling pathways involved. To carry out the study, we collected colonic mucosal biopsy samples from UC patients and control subjects. To investigate the spatial expression profile, we collected samples from the endoscopically inflamed and non-inflamed regions of same UC. We investigated the miRNA profile of inflamed and non-inflamed colonic biopsies by performing microarray and qRT-PCR. The potential targets of miRNA were predicted using bioinformatics tools such as TargetScan, MIRDB, DIANA-MicroT, microrna.org and Pictar. The pathways involved were identified by mirPath v.3:DIANA TOOLS. We found significantly increased expression of miR-125b, miR-223, miR-155 and miR-138 in the inflamed vs. non inflamed as well as in the inflamed vs. controls. MiR-223 showed significantly increased expression in the inflamed as well as non-inflamed mucosa as compared with controls which indicates towards the disease independent behaviour of this miRNA. When the potential targets of these miRNAs were analysed, they included the genes involved in the major inflammatory pathways such as NFkB pathway and MAPK signalling. TRAF6 which is targeted by miR-125b and a critical signalling molecule in the conventional NFkB pathway showed a significant downregulation in the UC patients. Similarly IKKα, potential target of miR-223 and part of non-conventional NFkB pathway showed a significant down-regulation. Our study indicate towards the spatial expression of miR-125b, miR-223, miR-138, and miR-155 in the inflamed and non-inflamed pockets of same UC patients, which suggest miRNA as one of the contributing factor in pathogenesis of UC. MiR-223 showed a disease independent behaviour therefore, it could be developed as a biomarker for UC. Studying these miRNA and the signalling pathways in detail, could provide better insight of disease pathogenesis and provide scope for their use in therapeutics.