Expression alteration of long non-coding RNAs and their target genes in the intestinal mucosa of patients with Crohn's disease
Expression alteration of long non-coding RNAs and their target genes in the intestinal mucosa of patients with Crohn's disease
复制标题
克罗恩病患者肠粘膜中长非编码RNA及其靶基因的表达变化
DOI：
10.1016/j.cca.2019.02.031
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发表时间：
2019-07-01
影响因子：
5
通讯作者：
Shi, Ruihua
中科院分区：
文献类型：
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作者：
Li, Na;Shi, Ruihua
背景：克罗恩病（Crohn's Disease，CD）是一种慢性特发性胃肠道炎症性疾病。它在世界范围内不断增加，已成为全球性的健康问题。CD发生的关键病理机制尚未确定，目前的治疗大多是抗症状治疗，疗效有限。本研究旨在探讨lncRNAs是否参与CD的发病机制，以及它们在CD发病过程中如何调控靶基因。方法：收集2017年5月至2018年5月在东南大学附属中大医院确诊的CD患者。收集病理和正常肠粘膜，提取总RNA，用lncRNA和mRNA基因芯片分析lncRNA和mRNA的表达。对差异显著（>= 10倍，P < 0.05）的lncRNA和mRNA进行鉴定和验证。通过CNC分析揭示了与差异表达的lncRNA共表达的mRNA。通过使用miRbase、Targetscan和NCBI数据库的Ce（cis/tans）机制分析来确定潜在的调节因子。结果：8种lncRNA在回肠末端病变黏膜和正常黏膜中差异表达。差异表达lncRNA的CNC分析显示50个具有正或负调控的共表达mRNA。基于mRNA KEGG通路分析，它们中的大多数似乎参与细胞信号传导通路。细胞质中有6个lncRNA参与Ce调控机制，细胞核中有2个lncRNA参与顺反调控机制。最后，通过CNC、KEGG富集分析和Ce（trans-cis）分析，得到了lncRNAs-miRNAs和TFs-mRNAs之间的三元关系。结论：lncRNAs在CD黏膜中的差异表达，提示lncRNAs参与了免疫反应。这些lncRNA可能通过lncRNA-miRNAs/TFs-mRNAs的遗传网络参与肠粘膜功能的调节。
Background: CD(Crohn's Disease)is a chronic idiopathic inflammatory disorders of the GI tract. It is increasing worldwide and has become a global health problem. The key pathological mechanism for CD occurrence has not been identified, and present treatments are mostly anti-symptom therapy, which has limited efficacy. In this study, we investigate whether lncRNAs are involved in the pathogenesis of CD and how they may regulate the target genes in CD process.Methods: CD patients were diagnosed in Zhongda Hospital of Southeast University between May 2017 and May 2018. Pathological and normal intestinal mucosa were collected and total RNA was extracted the expression of lncRNA and mRNA was profiled and analyzed by using lncRNA and mRNA gene chips. The lncRNAs and mRNAs with significant alternations (>= 10 times and P < 0.05) were identified and verified. The co-expressed mRNAs with the differentially expressed lncRNAs were revealed by CNC analysis. The potential regulatory factors were determined by the Ce (cis/tans) mechanism analysis with the use of miRbase, Targetscan, and NCBI database. Finally, the lncRNA-miRNA/TF-mRNA expression network was predicted.Results: Eight lncRNAs were found to be differentially expressed between the pathological mucosa and the normal mucosas in the ileal end. CNC analysis of the differentially expressed lncRNAs revealed fifty co-expressed mRNAs with positive or negative regulation. Base on the mRNAs KEGG pathway analysis, most of them appeared to be involved in cell signaling pathways. Six lncRNAs in the cytoplasm participated in the Ce mechanism, and the rest two lncRNAs in the nucleus participated in the cis/trans regulation mechanism. Finally, ternary relationship of lncRNAs-miRNAs and TFs-mRNAs was obtained by CNC,KEGG enrichment analysis and Ce (trans/cis) analysis.Conclusion: The differential expression of lncRNAs in CD mucosa indicated that lncRNAs were involved in immune reaction. These lncRNAs might contribute to the regulation of intestinal mucosa function through the genetic network of lncRNAs -miRNAs/TFs-mRNAs.