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炎症性肠病患儿黏膜微小RNA表达的改变

Altered mucosal expression of microRNAs in pediatric patients with inflammatory bowel disease.

作者信息

Béres Nóra Judit, Kiss Zoltán, Sztupinszki Zsófia, Lendvai Gábor, Arató András, Sziksz Erna, Vannay Ádám, Szabó Attila J, Müller Katalin Eszter, Cseh Áron, Boros Kriszta, Veres Gábor

机构信息

1st Department of Pediatrics, Semmelweis University, Budapest, Hungary.

MTA-SE Tumor Progression Research Group, Budapest, Hungary.

出版信息

Dig Liver Dis. 2017 Apr;49(4):378-387. doi: 10.1016/j.dld.2016.12.022. Epub 2016 Dec 27.

Abstract

INTRODUCTION

MicroRNAs (miRs) came recently into focus as promising novel research targets offering new insights into the pathogenesis of inflammatory bowel diseases (IBD).

AIMS

The aim of our study was to identify a pediatric IBD (pIBD) characteristic miR profile serving as potential Crohn's disease (CD) and ulcerative colitis (UC) specific diagnostic pattern and to further analyze the related target genes.

METHODS

Small RNA sequencing was performed on inflamed and intact colonic biopsies of CD, and control patients. Selected miRs were further investigated by RT-PCR, complemented with an UC group, in order to address the differential diagnostic potential of miRs in the two IBD subtypes. To analyze network connection of differentially expressed miRs and their target genes MiRTarBase database and previous transcriptome sequencing data from pediatric patient groups were used.

RESULTS

Sequencing analysis identified 170 miRs with altered expression. RT-PCR analysis revealed altered expression of miR-31, -125a, -142-3p, and -146a discriminating between the inflamed mucosa of CD and UC. In the intact mucosa of CD patients the expression of miR-18a, -20a, -21, -31, -99a, -99b, -100, -125a, -126, -142-5p, -146a, -185, -204, -221, and -223 was elevated compared to the controls. The expression of miR-20a, -204 and -221 was elevated exclusively in the intact region of CD patients compared to the controls. Enrichment analysis identified main IBD-related functional groups.

CONCLUSIONS

We demonstrated a characteristic colonic miR pattern in pIBD that could facilitate deeper understanding of the pathomechanism of IBD and may serve as a diagnostic tool.

摘要

引言

微小RNA(miR)最近成为有前景的新型研究靶点,为深入了解炎症性肠病(IBD)的发病机制提供了新视角。

目的

本研究旨在确定一种儿童IBD(pIBD)特征性miR谱,作为潜在的克罗恩病(CD)和溃疡性结肠炎(UC)特异性诊断模式,并进一步分析相关靶基因。

方法

对CD患者及对照患者的炎症性和完整结肠活检组织进行小RNA测序。通过RT-PCR对选定的miR进行进一步研究,并补充UC组,以探讨miR在两种IBD亚型中的鉴别诊断潜力。为分析差异表达miR及其靶基因的网络连接,使用了MiRTarBase数据库和来自儿科患者组的先前转录组测序数据。

结果

测序分析鉴定出170个表达改变的miR。RT-PCR分析显示,miR-31、-125a、-142-3p和-146a的表达改变可区分CD和UC的炎症黏膜。在CD患者的完整黏膜中,与对照组相比,miR-18a、-20a、-21、-31、-99a、-99b、-100、-125a、-126、-142-5p、-146a、-185、-204、-221和-223的表达升高。与对照组相比,miR-20a、-204和-221的表达仅在CD患者的完整区域升高。富集分析确定了主要的IBD相关功能组。

结论

我们在pIBD中证明了一种特征性结肠miR模式,这有助于更深入地了解IBD的发病机制,并可能作为一种诊断工具。

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