Introduction MicroRNAs (miRNAs) are becoming increasingly recognised as key players in a multitude of inflammatory pathways through their ability to regulate gene expression. Numerous miRNAs have been shown to have an abnormal expression in Ulcerative Colitis (UC), although published results are inconsistent possibly due to the grouping of different phenotypes and concomitant medication. Understanding the miRNA profile in homogeneous groupings is a major advance to understanding the mechanisms that underpin the aetiology of UC. The aim is to identify a distinctive miRNA signature for active sigmoid UC in patients who are treatment naïve.
Methods Sigmoid biopsies were taken from patients with Baron Grade 3 active UC (n=21), patients with previous sigmoid UC who have no inflammation (n=15) and healthy controls (n=20). All patients were matched for age, sex, ethnicity and no medication for ≥6 months. Deregulated miRNA candidates were first identified in active UC (n=6) and compared against controls (n=6) using Taqman® Array MicroRNA card A. Array cards were performed in pairs (active vs control). The differential expression of 377 miRNAs were calculated for each pair. The 20 miRNAs with the greatest increase and 20 with the greatest decrease in expression for each pair were then compared with the other array card pairs. MiRNAs that had a consistently increased or decreased expression in all array card pairs were validated using RT-qPCR. Differential expressions was calculated using the fold change compared with healthy controls. Statistical analysis was performed using Mann–Whitney test
Results Seven miRNAs were consistently deregulated across all miRNA array pairs. RT-qPCR confirmed a significantly increased fold change in three miRNAs; miR-31 (10.97, p<0.001), miR-223 (3.45, p<0.001) and miR-146b-5p (2.26, p=0.002). Four miRNAs were shown to have a statistically significant decreased expression by RT-qPCR. Only miR-31 and -223 were deregulated with statistical significance in inactive UC (fold increase of 2.83, p<0.001 and 2.47, p<0.001 respectively).
Conclusion (1) A distinct subset of miRNAs is deregulated in the mucosa of actively inflamed sigmoid UC in patients who are on no treatment. (2) miR-31 and -223 are constitutionally expressed in sigmoid UC and could offer a potential diagnostic tool for patients who have no active inflammation at the time of endoscopy. (3) Manipulating miRNA expression offers promise as a potential new therapeutic pathway in active disease. (4) When investigating miRNA profiles and function it is essential to use an accurately phenotyped and homogeneous patient group. (5) We are the first to show a miRNA profile for sigmoid UC in treatment naive patients.
Competing interests None declared.
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