Altered mucosal expression of microRNAs in pediatric patients with inflammatory bowel disease
Altered mucosal expression of microRNAs in pediatric patients with inflammatory bowel disease
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DOI：
10.1016/j.dld.2016.12.022
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发表时间：
2017-04-01
影响因子：
4.5
通讯作者：
Veres, Gabor
中科院分区：
文献类型：
--
作者：
Beres, Nra Judit;Kiss, Zoltan;Veres, Gabor
简介：MicroRNA (miR) 最近成为有前途的新研究靶点，为炎症性肠病 (IBD) 的发病机制提供新的见解。目的：我们研究的目的是确定儿科 IBD (pIBD) 特征 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 的发炎和完整结肠活检进行小 RNA 测序，并进行对照患者。通过 RT-PCR 进一步研究选定的 miR，并辅以 UC 组，以解决 miR 在两种 IBD 亚型中的差异诊断潜力。为了分析差异表达的 miR 及其靶基因的网络连接，使用了 MiRTarBase 数据库和儿科患者组先前的转录组测序数据。结果：测序分析识别出 170 个表达发生改变的 miR。 RT-PCR 分析显示 miR-31、-125a、-142-3p 和 -146a 的表达发生变化，可区分 CD 和 UC 的发炎粘膜。在CD患者的完整粘膜中，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，CD 患者的完整区域中 miR-20a、-204 和 -221 的表达仅升高。富集分析确定了主要的 IBD 相关功能组。结论：我们证明了 pIBD 中的特征性结肠 miR 模式，可以促进更深入地了解 IBD 的病理机制，并可以作为诊断工具。 (C) 2016 年由 Elsevier Ltd 代表 Editrice Gastroenterologica Italiana S.r.l. 出版。
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. (C) 2016 Published by Elsevier Ltd on behalf of Editrice Gastroenterologica Italiana S.r.l.