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Construction and Comprehensive Analysis of Dysregulated Long Noncoding RNA-Associated Competing Endogenous RNA Network in Moyamoya Disease.
Computational and Mathematical Methods in Medicine ( IF 2.809 ) Pub Date : 2020-06-13 , DOI: 10.1155/2020/2018214
Xuefeng Gu 1, 2 , Dongyang Jiang 3 , Yue Yang 4, 5 , Peng Zhang 6 , Guoqing Wan 1, 2 , Wangxian Gu 2 , Junfeng Shi 2 , Liying Jiang 2 , Bing Chen 7 , Yanjun Zheng 2 , Dingsheng Liu 8 , Sufen Guo 4, 5 , Changlian Lu 2
Affiliation  

Background. Moyamoya disease (MMD) is a rare cerebrovascular disease characterized by chronic progressive stenosis or occlusion of the bilateral internal carotid artery (ICA), the anterior cerebral artery (ACA), and the middle cerebral artery (MCA). MMD is secondary to the formation of an abnormal vascular network at the base of the skull. However, the etiology and pathogenesis of MMD remain poorly understood. Methods. A competing endogenous RNA (ceRNA) network was constructed by analyzing sample-matched messenger RNA (mRNA), long non-coding RNA (lncRNA), and microRNA (miRNA) expression profiles from MMD patients and control samples. Then, a protein-protein interaction (PPI) network was constructed to identify crucial genes associated with MMD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were employed with the DAVID database to investigate the underlying functions of differentially expressed mRNAs (DEmRNAs) involved in the ceRNA network. CMap was used to identify potential small drug molecules. Results. A total of 94 miRNAs, 3649 lncRNAs, and 2294 mRNAs were differentially expressed between MMD patients and control samples. A synergistic ceRNA lncRNA-miRNA-mRNA regulatory network was constructed. Core regulatory miRNAs (miR-107 and miR-423-5p) and key mRNAs (STAT5B, FOSL2, CEBPB, and CXCL16) involved in the ceRNA network were identified. GO and KEGG analyses indicated that the DEmRNAs were involved in the regulation of the immune system and inflammation in MMD. Finally, two potential small molecule drugs, CAY-10415 and indirubin, were identified by CMap as candidate drugs for treating MMD. Conclusions. The present study used bioinformatics analysis of candidate RNAs to identify a series of clearly altered miRNAs, lncRNAs, and mRNAs involved in MMD. Furthermore, a ceRNA lncRNA-miRNA-mRNA regulatory network was constructed, which provides insights into the novel molecular pathogenesis of MMD, thus giving promising clues for clinical therapy.

中文翻译:

烟雾病中失调的长非编码RNA相关竞争性内源RNA网络的构建和综合分析。

背景。烟雾病(MMD)是一种罕见的脑血管疾病,其特征是双侧颈内动脉(ICA)、大脑前动脉(ACA)和大脑中动脉(MCA)慢性进行性狭窄或闭塞。MMD 继发于颅底异常血管网络的形成。然而,MMD 的病因和发病机制仍知之甚少。方法。通过分析 MMD 患者和对照样本的样本匹配信使 RNA (mRNA)、长非编码 RNA (lncRNA) 和 microRNA (miRNA) 表达谱,构建了竞争性内源 RNA (ceRNA) 网络。然后,构建了蛋白质-蛋白质相互作用(PPI)网络来识别与 MMD 相关的关键基因。将基因本体论 (GO) 和京都基因和基因组百科全书途径 (KEGG) 富集分析与 DAVID 数据库结合使用,研究 ceRNA 网络中涉及的差异表达 mRNA (DEmRNA) 的潜在功能。CMap 用于识别潜在的小药物分子。结果。MMD 患者和对照样本之间共有 94 个 miRNA、3649 个 lncRNA 和 2294 个 mRNA 存在差异表达。构建了协同的 ceRNA lncRNA-miRNA-mRNA 调控网络。确定了参与 ceRNA 网络的核心调控 miRNA(miR-107 和 miR-423-5p)和关键 mRNA(STAT5B、FOSL2、CEBPB 和 CXCL16)。GO和KEGG分析表明DEmRNA参与MMD免疫系统和炎症的调节。最后,两种潜在的小分子药物CAY-10415和靛玉红被CMap鉴定为治疗MMD的候选药物。结论。本研究利用候选 RNA 的生物信息学分析来识别一系列与 MMD 相关的明显改变的 miRNA、lncRNA 和 mRNA。此外,构建了ceRNA lncRNA-miRNA-mRNA调控网络,为MMD的新分子发病机制提供了见解,从而为临床治疗提供了有希望的线索。
更新日期:2020-06-13
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