Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 7, 2017; 23(29): 5324-5332
Published online Aug 7, 2017. doi: 10.3748/wjg.v23.i29.5324
MicroRNA exhibit altered expression in the inflamed colonic mucosa of ulcerative colitis patients
Swati Valmiki, Vineet Ahuja, Jaishree Paul
Swati Valmiki, Jaishree Paul, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India
Vineet Ahuja, Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi 110029, India
Author contributions: Valmiki S and Paul J designed the study, analyzed the data and wrote the manuscript; Valmiki S performed the experiments; Ahuja V provided the samples with clinical history.
Supported by Department of Biotechnology, Ministry of Science and Technology, New Delhi, Government of India vide BT/PR8348/MED/30/1023/2013 to Paul J; PURSE grant from the Department of Science and Technology, New Delhi India vide 6(54) SLS/JP/DST PURSE/2015-2016.
Institutional review board statement: The study has been ethically approved from the Institute Ethics Committee, All India Institute of Medical Sciences (Ref. No. T-290/23.06.2015, RT-7/27.01.2016) and Institutional Ethics Review Board, JNU (IERB Ref. No.2016/Student/93).
Conflict-of-interest statement: The authors declare no conflict of interest in the present study.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Jaishree Paul, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India. jaishree@mail.jnu.ac.in
Telephone: +91-11-26704156 Fax: +91-11-26742558
Received: February 7, 2017
Peer-review started: February 8, 2017
First decision: March 30, 2017
Revised: May 22, 2017
Accepted: June 1, 2017
Article in press: June 1, 2017
Published online: August 7, 2017
Processing time: 180 Days and 18.8 Hours
Abstract
AIM

To investigate the miRNA expression in colonic mucosal biopsies from endoscopically inflamed and non inflamed regions of ulcerative colitis (UC) patients.

METHODS

Colonic mucosal pinch biopsies were analyzed from the inflamed and non inflamed regions of same UC patient. Total RNA was isolated and differential miRNA profiling was done using microarray platform. Quantitative Real Time PCR was performed in colonic biopsies from inflamed (n = 8) and non-inflamed (n = 8) regions of UC and controls (n = 8) to validate the differential expression of miRNA. Potential targets of dysregulated miRNA were identified by using in silico prediction tools and probable role of these miRNA in inflammatory pathways were predicted.

RESULTS

The miRNA profile of inflamed colonic mucosa differs significantly from the non-inflamed. Real time PCR analysis showed that some of the miRNA were differentially expressed in the inflamed mucosa as compared to non inflamed mucosa and controls (miR-125b, miR-223, miR-138, and miR-155), while (miR-200a) did not show any significant changes. In contrast to microarray, where miR-378d showed downregulation in the inflamed mucosa, qRT-PCR showed a significant upregulation in the inflamed mucosa as compared to the non inflamed. The in silico prediction analysis revealed that the genes targeted by these miRNAs play role in the major signaling pathways like MAPK pathway, NF-κB signaling pathway, cell adhesion molecules which are all assciated with UC.

CONCLUSION

The present study reports disease specific alteration in the expression of miR-125b, miR-155, miR-223 and miR-138 in UC patients and also predict their biological significance.

Keywords: Ulcerative colitis; Colon mucosa; MicroRNA; Microarray; qRT-PCR; In silico analysis

Core tip: In order to get an insight into the pathogenesis of ulcerative colitis (UC), we explored spatial expression of microRNA in the inflamed and non-inflamed region of mucosal tissue of patients. Profiling of differentially expressed miRNA was generated by microarray from three paired samples. Few significantly dysregulated microRNA were validated using qRT-PCR. The present study reports disease specific alteration in the expression of miR-125b, miR-155, miR-223 and miR-138 in UC patients and also analyzed their biological significance using in silico tools. MiR-223 exhibited elevated expression independent of disease activity therefore, could be a potential candidate as biomarker for UC.