Objective: This study aimed to investigate the possible molecular mechanisms associated with ischemic stroke through the construction of a lncRNA-miRNA-mRNA network. miRNA expression profile in GSE55937, mRNA and lncRNA expression profiles in GSE122709, and mRNA expression profile in GSE146882 were downloaded from the NCBI GEO database. After the identification of the differentially expressed miRNA, lncRNA, and mRNA using GSE55937 and GSE122709 in ischemic stroke vs. control groups, a protein-protein interaction network was constructed. The lncRNA-miRNA, lncRNA-mRNA, and miRNA-mRNA pairs were predicted, and a lncRNA-miRNA-mRNA network was constructed. Additionally, the gene-drug interactions were predicted. Characteristic genes were used to construct a support vector machine (SVM) model and verified using quantitative reverse transcription polymerase chain reaction. In total 38 miRNAs, 115 lncRNAs, and 990 mRNAs were identified between ischemic stroke and control groups. A PPI network with 371 nodes and 2306 interaction relationships was constructed. The constructed lncRNA-miRNA-mRNA network contained 7 mRNAs, 14 lncRNAs, such as SND1-IT1, NAPA-AS1, LINC01001, LUCAT1, and ASAP1-IT2, and 8 miRNAs, such as miR-93-3p and miR-24-3p. The drug action analysis of the seven differential mRNAs included in the lncRNA-miRNA-mRNA network showed that four genes (GPR17, ADORA1, OPRM1 and LPAR3) were predicted as molecular targets of drugs. The AUC of the constructed SVM model was 0.886. The verification results of the relative expression of RNA by qRT-PCR were consistent with the results of bioinformatics analysis. LPAR3, ADORA1, GPR17, and OPRM1 may serve as therapeutic targets of ischemic stroke. lncRNA-miRNA-mRNA regulatory axis such as SND1-IT1/NAPA-AS1/LINC01001-miR-24-3p-LPAR3/ADORA1 and LUCAT1/ASAP1-IT2-miR-93-3p-GPR17 may play important roles in the progression of ischemic stroke.

中文翻译：

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使用 miRNA、mRNA 和 lncRNA 表达谱的综合分析阐明缺血性中风的分子机制

目的：本研究旨在通过构建lncRNA-miRNA-mRNA网络，探讨缺血性脑卒中可能的分子机制。GSE55937中的miRNA表达谱、GSE122709中的mRNA和lncRNA表达谱以及GSE146882中的mRNA表达谱从NCBI GEO数据库下载。在使用 GSE55937 和 GSE122709 鉴定缺血性卒中组与对照组差异表达的 miRNA、lncRNA 和 mRNA 后，构建了蛋白质-蛋白质相互作用网络。预测lncRNA-miRNA、lncRNA-mRNA和miRNA-mRNA对，构建lncRNA-miRNA-mRNA网络。此外，还预测了基因-药物相互作用。特征基因用于构建支持向量机（SVM）模型，并使用定量逆转录聚合酶链反应进行验证。在缺血性卒中组和对照组之间共鉴定出 38 个 miRNA、115 个 lncRNA 和 990 个 mRNA。构建了一个包含 371 个节点和 2306 个交互关系的 PPI 网络。构建的lncRNA-miRNA-mRNA网络包含7个mRNA，14个lncRNA，如SND1-IT1、NAPA-AS1、LINC01001、LUCAT1和ASAP1-IT2，以及8个miRNA，如miR-93-3p和miR-24- 3 点。lncRNA-miRNA-mRNA网络中包含的7个差异mRNA的药物作用分析表明，4个基因（GPR17、ADORA1、OPRM1和LPAR3）被预测为药物的分子靶点。构建的 SVM 模型的 AUC 为 0.886。qRT-PCR对RNA相对表达量的验证结果与生物信息学分析结果一致。LPAR3、ADORA1、GPR17 和 OPRM1 可作为缺血性卒中的治疗靶点。lncRNA-miRNA-mRNA 调控轴，如 SND1-IT1/NAPA-AS1/LINC01001-miR-24-3p-LPAR3/ADORA1 和 LUCAT1/ASAP1-IT2-miR-93-3p-GPR17 可能在缺血性中风。