DOP013. Pre-treatment differential microRNA expression profile in ulcerative colitis patients according to their response to corticosteroids
J.E. Naves1, J. Mañe1, V. Loren1, M. Mañosa1, I. Moret2, A. García-Jaraquemada1, G. Bastida2, E. Cabré1, B. Beltrán2, E. Domènech1, 1Hospital Universitari Germans Trias i Pujol, Gastroenterology, Badalona, Spain, 2Hospital Universitari I Politècnic La Fe, Valencia, Gastroenterology, Valencia, Spain
Corticosteroids (CS) remain the first-line treatment for moderate-to-severe active ulcerative colitis (UC). However, up to 40% of patients do not have an adequate response, an event that to date, cannot be predicted yet. MicroRNA (miRNA) are small non-coding RNA fragments that modulate gene expression at posttranscriptional level, thus playing a critical role in many biological processes. Little is known about the influence of miRNA in the response to CS in UC. The objetive of our study was to compare the miRNA profile in rectal mucosa of patients with active UC responding and non-responding to CS.
Rectal biopsies were obtained from consecutive UC patients before starting CS therapy for a moderate-to-severe flare. Patients were grouped according to clinical response (non-responder = moderate or severe activity according to Montreal's classification at day 7 or need for rescue therapy before day 7; responder = Less than moderate activity without need for rescue therapy at day 7). miRNA were identified by means of a sequencing method (TruSeq® SmallRNA kit from Illumina) on those fresh-frozen rectal biopsies that reached a RNA Integrity Number (RIN) ≥8. Comparison of miRNA profile between groups was carried out on the miRanalyzer D.E. tool through DESeq package. Those miRNA with a fold change ≥1.5 and adjusted p-value ≤0.05 were further studied. Potential targets of selected miRNA were checked in “Target Human Scan database” (www.targetscan.org), and their impact on biological activity was searched in “GeneCodis database” (http://genecodis.cnb.csic.es).
15 out of 24 tissue samples (8 responders and 7 non-responders) reached a RIN value ≥8 allowing miRNA sequencing. We found more than 1,300 known miRNA and about 70 new miRNA. Responders to CS had an up-regulated expression of has-miR-5701 and has-miR-625–3p, and down-regulated expression of has-miR-1246 and has-miR-1291 as compared to non-responders. Bioanalysis using miRNA targets database showed up to 2,000 potential targets for the aforementioned miRNA, most of them involved in MAPK signalling pathways, cytoskeleton organization pathway, and cell differentiation endocytosis and autophagy mechanisms.
Patients with active UC not responding to CS show a differential mucosal miRNA expression profile before starting therapy. These findings suggest that regulation of gene expression by miRNA might play a role in the response to treatment in UC patients.