Circulating mRNA and microRNA profiling analysis in patients with ischemic stroke.

Abstract

To provide insight into molecular diagnosis and individualized treatment of ischemic stroke (IS), several available datasets in IS were analyzed to identify the differentially expressed genes and microRNAs (miRNAs). Series matrix files from GSE22255 and GSE16561 (mRNA profiles), a well as GSE110993 (miRNA profile) were downloaded from the Gene Expression Omnibus database. System‑level clustering was performed with GeneCluster 3.0 software, and gene annotation and pathway enrichment were performed with gene ontology analysis and Database for Annotation, Visualization and Integrated Discovery software. For a protein‑protein interaction (PPI) network, Biological General Repository for Interaction Datasets and IntAct interaction information were integrated to determine the interaction of differentially expressed genes. The selected miRNA candidates were imported into the TargetScan, miRDB and miRecords databases for the prediction of target genes. The present study identified 128 upregulated and 231 downregulated genes in female stroke patients, and 604 upregulated and 337 downregulated genes in male stroke patients compared with sex‑ and age‑matched controls. The construction of a PPI network demonstrated that male stroke patients exhibited YWHAE, CUL3 and JUN as network center nodes, and in female patients CYLD, FOS and PIK3R1 interactions were the strongest. Notably, these interactions are mainly involved in immune inflammatory response, apoptosis and other biological pathways, such as blood coagulation. Female and male upregulated genes were cross‑validated with another set of Illumina HumanRef‑8 v3.0 expression beadchip (GSE16561). Functional item association networks, gene function networks and transcriptional regulatory networks were successfully constructed, and the relationships between miRNAs and target genes were successfully predicted. The present study identified a number of transcription factors, including DEFA1, PDK4, SDPR, TCN1 and MMP9, and miRNAs, including miRNA (miR)‑21, miR‑143/145, miR‑125‑5p and miR‑122, which may serve important roles in the development of cerebral stroke and may be important molecular indicators for the treatment of IS.