MicroRNAs Expression in the Ileal Pouch of Patients with Ulcerative Colitis Is Robustly Up-Regulated and Correlates with Disease Phenotypes.

Abstract

Gene expression alterations are associated with disease behavior in inflammatory bowel disease (IBD). microRNAs (miRNAs) are dominant in the regulation of gene expression, and may affect IBD phenotype. Our aim was to assess mucosal miRNA expression in IBD and the correlation with intestinal inflammation.We performed a large-scale analysis of ileal mucosal miRNA. Biopsies were retrieved from patients with ileal Crohn's disease (CD), unoperated ulcerative colitis (UC) patients, UC patients after pouch surgery, and normal controls (NC). Pouch UC patients were classified as having a normal pouch (NP), chronic pouchitis (CP), and Crohn's-like disease of the pouch (CLDP). miRNA expression was analyzed by parallel massive (next-generation) sequencing (NGS). Bioinformatics tools were applied for clustering and the detection of potential targets.Sixty-one subjects were recruited. The ileum of unoperated UC patients was comparable with NC. There were significant miRNA expression alterations (fold change ≥2, corrected P ≤.05) in NP (n = 6), CP (n = 40) and CLDP (n = 139), but only two expression alterations were noted in CD. More than 90% of the altered miRNAs were up-regulated, and many were predicted to be associated with significantly decreased transcripts. miRNAs alterations were generally clustered with disease phenotypes.Ileal inflammation causes increased miRNA expression. miRNA alterations correlate with IBD phenotype, apparently by controlling the down-regulation of specific mRNAs.