Downregulation of miR-214-3p May Contribute to Pathogenesis of Ulcerative Colitis via Targeting STAT6.

Jin-An Li,Kui Wang,Zhen-Lan Wang,Dao-Yong Jia,Bi-Ying Yang,Chang-Bing Xiong,Yong-Duo Wang

doi:10.1155/2017/8524972

Jin-An Li, Kui Wang + Show 5 more

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https://doi.org/10.1155/2017/8524972

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Abstract

MicroRNAs (miRs) are small noncoding RNA molecules and recently have demonstrated that altered expression and functions are their tight association with ulcerative colitis (UC). Previous microarray study reported that miR-214 was downregulated in the sigmoid colon of patients with active UC, but the roles of miR-214 in the pathogenesis of UC remain to be elucidated. In this study, significant lower level of miR-214-3p and higher level of STAT6 in the intestinal mucosa of active UC patients compared with the health controls were confirmed by quantitative real-time PCR. Results of luciferase reporter assays and western blot demonstrated that miR-214-3p directly targets STAT6 and negatively regulates the expression of STAT6 at the posttranscriptional level. Furthermore, the expression of miR-214-3p was decreased in TNF-α treated HT29 cells and STAT6 protein level was increased in a time-dependent manner. Silenced STAT6 and upregulation of miR-214-3p could decrease the level of INF-γ in TNF-α treated HT29 cells. Additionally, the results of the present study indicate that miR-214-3p and STAT6 axis may be a novel therapeutic target for intestinal inflammation of patients with active UC.

Highlights

Ulcerative colitis (UC) is a common inflammatory bowel disease (IBD), and bloody purulent stool, recurrent diarrhea, and abdominal pain are the main clinical manifestations [1]
Available data indicated that many studies have focused on expression and functions of miRs in kinds of IBD, especially in UC [4]. miRs are small noncoding RNA oligonucleotides and endogenous and short single stranded molecules that have emerged as key regulators of biological and pathological processes, involved in the pathogenesis of different human inflammatory diseases
Decreased miR-214-3p and Increased STAT6 Are Detected in the Intestinal Mucosa of UC Patients

Summary

Introduction

Ulcerative colitis (UC) is a common inflammatory bowel disease (IBD), and bloody purulent stool, recurrent diarrhea, and abdominal pain are the main clinical manifestations [1]. Increasing evidences have suggested that miRs play important roles in the regulation of intestinal inflammation in UC. MiR-16 was proved to play a regulative role in the immune and inflammatory responses via suppressing the expression of the A2aAR to control the activation of the NF-κB signaling pathway in ulcerative colitis [6]. Exploring the role of certain miRs in the regulation of intestinal inflammation may be conducive to understanding the pathogenesis of UC. We demonstrated that miR-214-3p played an important role in the regulation of intestinal inflammation. These findings suggested that miR214-3p could provide a theoretical basis for further study on the pathogenesis and new treatment for UC

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