P042 Response to corticosteroids in Ulcerative Colitis may be related to modulation of mTOR signaling pathway genes by microRNAs
J.E. Naves*1, J. Manye1, 2, V. Loren1, M. Mañosa2, 3, I. Moret2, 4, A. García-Jaraquemada1, G. Bastida2, 4, B. Beltrán2, 4, E. Cabré2, 3, E. Domènech2, 3
1Germans Trias i Pujol Health Sciences Research Institute, Gastroenterology Department, Badalona, Spain, 2Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, CIBERehd, , Spain, 3Hospital Universitari Germans Trias i Pujol, Gastroenterology Department, Badalona, Spain, 4Hospital La Fe, Gastroenterology Unit, Valencia, Spain
Up to 40% of patients with active Ulcerative Colitis (UC) do not have an adequate response to corticosteroids (CS). Mechanisms of resistance to CS in UC are not well understood. MicroRNA (miR) are small non-coding RNA fragments that modulate messenger RNA (RNAm) at a post-transcriptional level, playing a critical role in many biological processes. Little is known about the influence of miR in the response to CS in UC. Objective: To compare the transcriptomic profile (miR and RNAm) in rectal mucosa of patients with active UC responding and non-responding to CS.
Rectal biopsies were obtained from UC patients before and after three days of CS treatment for a moderate-to-severe flares. Patients were grouped according to clinical response (non-responder = moderate or severe activity according to Montreal's classification or need of rescue therapy at day 7; responder = mild activity or remission without rescue therapy at day 7). miR were identified by means of a sequencing method (Tru Seq Small RNA kit from Illumina) and RNAm were study by microarrays method (HumanHT-12 kit from Illumina) on those rectal biopsies with high integrity. After the comparison between groups those miR and RNAm with a fold change greater than 1.5 and adjusted p-value less than 0.05 were further studied. Potential targets of selected miR were checked in "Target Human Scan database" (
8 responders and 7 non-responders tissue samples reached an integrity that allowed miR sequencing and microarrays study. Comparison between responders and non-responders before CS showed a differential miR expression of miR-1246, miR-1291, miR-5701 and miR-625-3p. Comparison between responders before and after treatment showed differential expression of miR-183-5p, miR-3607-3p, miR-1246, miR-5701 and miR-625-3p. And comparison between non-reponders before and after treatment showed differential expression of miR-4770, miR-449, miR-145-3p, miR-1246 and miR-1291. The only gene with differential expression after microarrays study was DDIT4, which was down-regulated in responders before CS in comparison with responders after 3 days of treatment. A further in silico study reveals that DDIT4 is a potential target of three of the differential expressed miR (miR-183-5p, miR-625-3p , miR-3607-3p) and also that this gene is linked to the mTOR pathway (and indirectly with autophagy).
There is a different miR profile in rectal mucosa of patients with active UC responding and non-reponding to CS. Our findings suggest that regulation of mTOR and autofagy pathways by miR might be involved in the response to CS in active UC.
- Posted in: Poster presentations: Basic Science (2015)