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基于竞争性内源性RNA的lncRNA-miRNA-mRNA网络的重建与分析揭示类风湿关节炎中的功能性lncRNA

Reconstruction and analysis of the lncRNA-miRNA-mRNA network based on competitive endogenous RNA reveal functional lncRNAs in rheumatoid arthritis.

作者信息

Jiang Hui, Ma Rong, Zou Shubiao, Wang Yongzhong, Li Zhuqing, Li Weiping

机构信息

College of Basic Medicine, Anhui Medical University, 81 Meishan Road, Hefei, 230032, China.

Institute for Cardiovascular and Metabolic Disease, University of North Texas Health Sciences Center, 3500 Camp Bowie Boulevard, Fort Worth, 76107, USA.

出版信息

Mol Biosyst. 2017 Jun 1;13(6):1182-1192. doi: 10.1039/c7mb00094d. Epub 2017 May 4.

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease with an unknown etiology, occurring in approximately 1.0% of general population. More and more studies have suggested that long non-coding RNAs (lncRNAs) could play important roles in various biological processes and be associated with the pathogenesis of different kinds of diseases including RA. Although a large number of lncRNAs have been found, our knowledge of their function and physiological/pathological significance is still in its infancy. In order to reveal functional lncRNAs and identify the key lncRNAs in RA, we reconstructed a global triple network based on the competitive endogenous RNA (ceRNA) theory using the data from National Center for Biotechnology Information Gene Expression Omnibus and our previous paper. Meanwhile, Gene Ontology (GO) and pathway analysis were performed using Cytoscape plug-in BinGO and Database for Annotation, Visualization, and Integration Discovery (DAVID), respectively. We found that the lncRNA-miRNA-mRNA network was composed of 7 lncRNA nodes, 90 mRNA nodes, 24 miRNA nodes, and 301 edges. The functional assay showed that 147 GO terms and 23 pathways were enriched. In addition, three lncRNAs (S5645.1, XR_006437.1, J01878) were highly related to RA, and therefore, were selected as key lncRNAs. This study suggests that specific lncRNAs are associated with the development of RA, and three lncRNAs (S5645.1, XR_006437.1, J01878) could be used as potential diagnostic biomarkers and therapeutic targets.

摘要

类风湿性关节炎(RA)是一种病因不明的自身免疫性疾病,在普通人群中的发病率约为1.0%。越来越多的研究表明,长链非编码RNA(lncRNA)在各种生物学过程中发挥重要作用,并与包括RA在内的多种疾病的发病机制相关。尽管已经发现了大量的lncRNA,但我们对其功能以及生理/病理意义的了解仍处于起步阶段。为了揭示RA中具有功能的lncRNA并确定关键的lncRNA,我们利用来自美国国立生物技术信息中心基因表达综合数据库的数据以及我们之前论文的数据,基于竞争性内源RNA(ceRNA)理论重建了一个全局三重网络。同时,分别使用Cytoscape插件BinGO和注释、可视化与集成发现数据库(DAVID)进行基因本体(GO)和通路分析。我们发现lncRNA - miRNA - mRNA网络由7个lncRNA节点、90个mRNA节点、24个miRNA节点和301条边组成。功能分析表明,有147个GO术语和23条通路得到富集。此外,三个lncRNA(S5645.1、XR_006437.1、J01878)与RA高度相关,因此被选为关键lncRNA。本研究表明,特定的lncRNA与RA的发展相关,并且三个lncRNA(S5645.1、XR_006437.1、J01878)可作为潜在的诊断生物标志物和治疗靶点。

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