Response to corticosteroids in Ulcerative Colitis may be related to modulation of mTOR signaling pathway genes by microRNAs

Background: Mechanisms of resistance to corticosteroids (CS) in ulcerative colitis (UC) are not well understood. Little is known about the influence of microRNAs (miR) in the response to CS in UC. Objective: To compare the transcriptomic profile in rectal mucosa of patients with active UC responding and non-responding to CS. Methods: Rectal biopsies were obtained from UC patients before and after three days of CS treatment. Patients were grouped in responders and non-responders according to Montreal’s classification. miR were identified by means of a sequencing method (Illumina) and RNAm were study by microarrays method (Illumina) on those rectal biopsies with high integrity. Those miR and RNAm with a fold change ≥ 1.5 and adjusted p-value ≤ 0.05 were further studied. Results: 32 out of 48 tissue samples reached an integrity that allowed miR sequencing or microarrays study. Comparison between groups showed a differential miR expression of miR-1246, miR-1291, miR-5701 and miR-625-3p, miR-183-5p, miR-3607-3p, miR-4770, miR-449, miR-145-3p. The only gene with differential expression after microarrays study was DDIT4. 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). Conclusion: There is a different profile of rectal microRNAs between responders and non-responders to CS. Our findings suggest that regulation of mTOR and autophagy pathways by miR might be involved in the response to CS in active UC.