Exploration of potential therapeutic targets for stroke based on the GEO database.
Exploration of potential therapeutic targets for stroke based on the GEO database.
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基于GEO数据库探索脑卒中潜在治疗靶点
DOI：
10.21037/atm-21-5815
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发表时间：
2021-12
影响因子：
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通讯作者：
Deng QL
中科院分区：
文献类型：
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作者：
Ma LZ;Dong LW;Zhu J;Yu JS;Deng QL
本研究旨在分析非编码RNA测序结果，筛选差异表达的长链非编码RNA (lncRNAs)，并预测lncRNA靶基因。进一步阐明lncrna的潜在功能，从而探索脑卒中的潜在生物标志物和治疗靶点。方法从Gene Expression Omnibus （GEO）数据库下载脑卒中患者和健康人血液样本（GSE102541和GSE140275）的LncRNA测序数据。本研究使用R软件及相关R包对测序结果进行批量校正和差异分析。它还筛选了差异表达的lncrna，并可视化了显著不同lncrna之间的相关性。通过StarBase数据库预测不同lncrna的靶基因。使用DAVID数据库对相关靶基因进行基因本体（GO）功能富集分析。根据脑卒中血液样本中差异最显著的lncrna表达水平进行主成分分析。结果本研究共筛选出239个差异表达lncrna，其中上调146个，下调93个。根据|log2FC|值由高到低，选出前10个差异最显著的lncrna。上调的lncrna为LINC02334、TARID、MRGPRF-AS1、CAI2、LINC00189、TUG1和RNF5P1。下调的lncrna包括AC005180.2、ADAMTS9-AS1和AC036108.3。TARID与MRGPRF-AS1密切相关。同时，LINC02334与TUG1呈强相关。CAI2、LINC00189和RNF5P1处于相关网络的核心，因此可能是卒中发病机制中的关键lncrna。GO功能富集结果显示，在肌肉收缩、RNA聚合酶II启动子转录调控、肌肉结构组成、局灶黏附、内皮细胞趋化、肌动蛋白、肌动蛋白细胞骨架、肌动蛋白丝结合、血糖调节、平滑肌收缩调节、骨骼肌细胞分化等功能中，基因显著富集。主成分分析显示，10个差异显著的lncrna能够显著区分脑卒中血液样本和健康对照血液样本，能够表征脑卒中的本质特征。结论LINC02334、TARID、MRGPRF-AS1、CAI2、LINC00189、TUG1、RNF5P1、AC005180.2、ADAMTS9-AS1、AC036108.3在脑卒中发病中发挥重要作用，可能是潜在的治疗靶点。
Background This study aimed to analyze non-coding RNA sequencing results, screen differentially expressed long non-coding RNAs (lncRNAs), and predict lncRNA target genes. It further clarifies the potential functions of lncRNAs, thus exploring potential biomarkers and therapeutic targets for stroke. Methods LncRNA sequencing data of blood samples from stroke patients and healthy subjects (GSE102541 and GSE140275) were downloaded from the Gene Expression Omnibus (GEO) database. This study used R software and related R packages to conduct a batch correction and differential analysis of sequencing results. It also screened differentially expressed lncRNAs and visualized the correlations between significantly different lncRNAs. Target genes of differential lncRNAs were predicted by the StarBase database. Gene ontology (GO) functional enrichment analysis of related target genes was performed using the DAVID database. Principal component analysis was performed based on the expression levels of lncRNAs with the most significant differences in stroke blood samples. Results A total of 239 differentially expressed lncRNAs were screened out in this study, of which 146 were upregulated and 93 were downregulated. According to |log2FC| values from highest to lowest, the top 10 lncRNAs with the most significant differences were selected. The upregulated lncRNAs were LINC02334, TARID, MRGPRF-AS1, CAI2, LINC00189, TUG1, and RNF5P1. The downregulated lncRNAs included AC005180.2, ADAMTS9-AS1, and AC036108.3. TARID was strongly correlated with MRGPRF-AS1. Meanwhile, LINC02334 was strongly correlated with TUG1. CAI2, LINC00189, and RNF5P1 were at the core of the correlation network and may therefore be the critical lncRNAs in stroke pathogenesis. GO functional enrichment results indicated that genes were significantly enriched in muscle contraction, RNA polymerase II promoter transcription regulation, muscle structure composition, focal adhesion, endothelial cell chemotaxis, actin, actin cytoskeleton, actin filament binding, blood lipid regulation, smooth muscle contraction regulation, skeletal muscle cell differentiation, and other functions. Principal component analysis showed that the 10 lncRNAs with significant differences could significantly distinguish stroke blood samples from healthy control blood samples, and could characterize the essential characteristics of stroke. Conclusions LINC02334, TARID, MRGPRF-AS1, CAI2, LINC00189, TUG1, RNF5P1, AC005180.2, ADAMTS9-AS1, and AC036108.3 play an essential role in the pathogenesis of stroke, and may be potential therapeutic targets.