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急性缺血性中风的潜在微小RNA生物标志物。

Potential microRNA biomarkers for acute ischemic stroke.

作者信息

Zeng Ye, Liu Jing-Xia, Yan Zhi-Ping, Yao Xing-Hong, Liu Xiao-Heng

机构信息

Institute of Biomedical Engineering, School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China.

State Key Laboratory of Oncology in South China, Department of Radiation Oncology, Sun Yat‑Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China.

出版信息

Int J Mol Med. 2015 Dec;36(6):1639-47. doi: 10.3892/ijmm.2015.2367. Epub 2015 Oct 12.

DOI:10.3892/ijmm.2015.2367
PMID:26459744
Abstract

Acute ischemic stroke is a significant cause of high morbidity and mortality in the aging population globally. However, current therapeutic strategies for acute ischemic stroke are limited. Atherosclerotic plaque is considered an independent risk factor for acute ischemic stroke. To identify biomarkers for carotid atheromatous plaque, bioinformatics analysis of the gene microarray data of plaque and intact tissue from individuals was performed. Differentially expressed genes (DEGs) were identified using the Multtest and Limma packages of R language, including 56 downregulated and 69 upregulated DEGs. Enriched microRNA (miRNA or miR) DEGs networks were generated using WebGestalt software and the STRING databases, and the miRNAs were validated using serum from acute ischemic stroke patients with reverse transcription quantitative PCR (RT‑qPCR). Four confirmed differentially expressed miRNAs (miR‑9, ‑22, ‑23 and ‑125) were associated with 28 upregulated DEGs, and 7 miRNAs (miR‑9, ‑30, ‑33, ‑124, ‑181, ‑218 and ‑330) were associated with 25 downregulated DEGs. Gene ontology (GO) function suggested that the confirmed miRNA‑targeted DEGs predominantly associated with signal transduction, the circulatory system, biological adhesion, striated muscle contraction, wound healing and the immune system. The confirmed miRNA‑targeted genes identified serve as potential therapeutic targets for acute ischemic stroke.

摘要

急性缺血性中风是全球老年人群中高发病率和高死亡率的重要原因。然而,目前急性缺血性中风的治疗策略有限。动脉粥样硬化斑块被认为是急性缺血性中风的独立危险因素。为了鉴定颈动脉粥样斑块的生物标志物,对个体斑块和完整组织的基因芯片数据进行了生物信息学分析。使用R语言的Multtest和Limma软件包鉴定差异表达基因(DEG),包括56个下调的DEG和69个上调的DEG。使用WebGestalt软件和STRING数据库生成富集的微小RNA(miRNA或miR)DEG网络,并使用急性缺血性中风患者的血清通过逆转录定量PCR(RT-qPCR)对miRNA进行验证。四个经证实差异表达的miRNA(miR-9、-22、-23和-125)与28个上调的DEG相关,7个miRNA(miR-9、-30、-33、-124、-181、-218和-330)与25个下调的DEG相关。基因本体(GO)功能表明,经证实的miRNA靶向DEG主要与信号转导、循环系统、生物粘附、横纹肌收缩、伤口愈合和免疫系统相关。经鉴定的经证实的miRNA靶向基因可作为急性缺血性中风的潜在治疗靶点。

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