MicroRNA-124 Regulates STAT3 Expression and Is Down-regulated in Colon Tissues of Pediatric Patients With Ulcerative Colitis

Koukos, G., Polytarchou, C. ORCID: 0000-0002-1948-7934, Kaplan, J.L., Morley–Fletcher, A., Gras–Miralles, B., Kokkotou, E., Baril–Dore, M., Pothoulakis, C., Winter, H.S. and Iliopoulos, D., 2013. MicroRNA-124 Regulates STAT3 Expression and Is Down-regulated in Colon Tissues of Pediatric Patients With Ulcerative Colitis. Gastroenterology, 145 (4), 842-852.e2. ISSN 0016-5085

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Abstract

Background & Aims - Altered levels and functions of microRNAs (miRs) have been associated with inflammatory bowel diseases (IBDs), although little is known about their roles in pediatric IBD. We investigated whether colonic mucosal miRs are altered in children with ulcerative colitis (UC). Methods - We used a library of 316 miRs to identify those that regulate phosphorylation of STAT3 in NCM460 human colonocytes incubated with interleukin-6. Levels of miR-124 were measured by real-time PCR analysis of colon biopsies from pediatric and adult patients with UC and patients without IBD (controls), and of HCT-116 colonocytes incubated with 5-aza-2’-deoxycytidine. Methylation of the MIR124 promoter was measured by quantitative methylation-specific PCR. Results - Levels of phosphorylated STAT3 and the genes it regulates (encoding VEGF, BCL2, BCLXL, and MMP9) were increased in pediatric patients with UC, compared to control tissues. Overexpression of miR-124, let-7, miR-125, miR-26, or miR-101 reduced STAT3 phosphorylation by ≥75% in NCM460 cells; miR-124 had the greatest effect. miR-124 was downregulated specifically in colon tissues from pediatric patients with UC and directly targeted STAT3 mRNA. Levels of miR-124 were decreased whereas levels of STAT3 phosphorylation increased in colon tissues from pediatric patients with active UC, compared to those with inactive disease. Furthermore, levels of miR-124 and STAT3 were inversely correlated in mice with experimental colitis. Downregulation of miR-124 in tissues from children with UC was attributed to hypermethylation of its promoter region. Incubation of HCT-116 colonocytes with 5-aza-2’ deoxycytidine upregulated miR-124 and reduced levels of STAT3 mRNA. Conclusions - MiR-124 appears to regulate the expression of STAT3. Reduced levels of miR-124 in colon tissues of children with active UC appear to increase expression and activity of STAT3, which could promote inflammation and pathogenesis of UC in children .

Item Type: Journal article
Publication Title: Gastroenterology
Creators: Koukos, G., Polytarchou, C., Kaplan, J.L., Morley–Fletcher, A., Gras–Miralles, B., Kokkotou, E., Baril–Dore, M., Pothoulakis, C., Winter, H.S. and Iliopoulos, D.
Publisher: Elsevier
Date: 2013
Volume: 145
Number: 4
ISSN: 0016-5085
Identifiers:
NumberType
10.1053/j.gastro.2013.07.001DOI
Divisions: Schools > School of Science and Technology
Depositing User: Linda Sullivan
Date Added: 03 Feb 2016 11:04
Last Modified: 09 Jun 2017 13:58
URI: http://irep.ntu.ac.uk/id/eprint/26874

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