Elucidating the Molecular Mechanism of Ischemic Stroke Using Integrated Analysis of miRNA, mRNA, and lncRNA Expression Profiles

Abstract

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 (PPI) 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 area under the curve 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.