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鉴定和验证与溃疡性结肠炎相关的关键 miRNA 和 miRNA-mRNA 调控网络。

Identification and Validation of Key miRNAs and a microRNA-mRNA Regulatory Network Associated with Ulcerative Colitis.

机构信息

Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China.

Key Laboratory of Hubei Province for Digestive System Disease, Renmin Hospital of Wuhan University, Wuhan, China.

出版信息

DNA Cell Biol. 2021 Feb;40(2):147-156. doi: 10.1089/dna.2020.6151. Epub 2020 Dec 21.

DOI:10.1089/dna.2020.6151
PMID:33347387
Abstract

Ulcerative colitis (UC) is a chronic, nonspecific, intestinal inflammatory disease that involves various genes and pathways in its pathogenesis. The current study revealed the key miRNAs and potential target gene regulatory network as a model for predicting the molecular mechanism of UC. This may provide novel insights for unraveling the pathogenesis of UC. Differentially expressed miRNAs (DEMIs) and mRNAs (differentially expressed genes [DEGs]) between UC patients and normal controls were screened using the Gene Expression Omnibus database. DEMI target genes were predicted using the miRDB, miRWalk, starBase, TarBase, and TargetScan databases, and an miRNA-mRNA network was established using DEGs that altered in opposition to DEMIs. We verified the expression of key DEMIs in a rodent UC model. The miRNA-mRNA network contained 31 DEMIs and 199 DEGs, which showed enrichment in inflammatory bowel disease. We selected 2 key miRNAs and 4 hub genes. In addition, we identified six DEMIs and genes from the preliminary validation analysis in model tissues. In the pathophysiological process of UC, various genes and proteins display expression differences and complex interactions with each other. These findings provide new insights into the potential key mechanisms associated with UC development.

摘要

溃疡性结肠炎(UC)是一种慢性、非特异性肠道炎症性疾病,其发病机制涉及多种基因和途径。本研究揭示了关键 miRNA 和潜在的靶基因调控网络,为预测 UC 的分子机制提供了模型。这可能为揭示 UC 的发病机制提供新的思路。利用基因表达综合数据库筛选 UC 患者和正常对照之间差异表达的 miRNA(DEMIs)和 mRNA(差异表达基因 [DEGs])。使用 miRDB、miRWalk、starBase、TarBase 和 TargetScan 数据库预测 DEMI 靶基因,并使用与 DEMIs 相反变化的 DEGs 构建 miRNA-mRNA 网络。我们验证了关键 DEMIs 在啮齿动物 UC 模型中的表达。miRNA-mRNA 网络包含 31 个 DEMI 和 199 个 DEG,这些基因在炎症性肠病中表现出富集。我们选择了 2 个关键 miRNA 和 4 个枢纽基因。此外,我们还从模型组织中的初步验证分析中鉴定了 6 个 DEMI 和基因。在 UC 的病理生理过程中,各种基因和蛋白质表现出表达差异,并相互之间存在复杂的相互作用。这些发现为 UC 发展相关的潜在关键机制提供了新的见解。

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