Identification of Hub Genes in the Pathogenesis of Ischemic Stroke Based on Bioinformatics Analysis

Abstract

Objective : The present study aimed to identify the function of ischemic stroke (IS) patients’ peripheral blood and its role in IS, explore the pathogenesis, and provide direction for clinical research progress by comprehensive bioinformatics analysis.Methods : Two datasets, including GSE58294 and GSE22255, were downloaded from Gene Expression Omnibus database. GEO2R was utilized to obtain differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs were performed using the database annotation, visualization and integrated discovery database. The protein-protein interaction (PPI) network of DEGs was constructed by search tool of searching interactive gene and visualized by Cytoscape software, and then the Hub gene was identified by degree analysis. The microRNA (miRNA) and miRNA target genes closely related to the onset of stroke were obtained through the miRNA gene regulatory network.Results : In total, 36 DEGs, containing 27 up-regulated and nine down-regulated DEGs, were identified. GO functional analysis showed that these DEGs were involved in regulation of apoptotic process, cytoplasm, protein binding and other biological processes. KEGG enrichment analysis showed that these DEGs mediated signaling pathways, including HTLV-I infection and microRNAs in cancer. The results of PPI network and cytohubba showed that there was a relationship between DEGs, and five hub genes related to stroke were obtained : SOCS3, KRAS, PTGS2, EGR1, and DUSP1. Combined with the visualization of DEG-miRNAs, hsa-mir-16-5p, hsa-mir-181a-5p and hsa-mir-124-3p were predicted to be the key miRNAs in stroke, and three miRNAs were related to hub gene.Conclusion : Thirty-six DEGs, five Hub genes, and three miRNA were obtained from bioinformatics analysis of IS microarray data, which might provide potential targets for diagnosis and treatment of IS.

Exploration of the Shared Gene Signatures and Molecular Mechanisms Between Ischemic Stroke and Atherosclerosis

“… 41 , 42 ZC3H12A is induced by cholesterol and is involved in cholesterol-induced HUVEC DNA damage that exacerbates atherosclerotic plaque formation; 43 , 44 Whereas studies have shown that upregulation of ZC3H12A expression has a mitigating effect on ischemic stroke, 45 however, the mechanism of ZC3H12A’s role in atherosclerosis and ischemic stroke needs further investigation. Previous Bioinformatics Analysis Shows Elevated KRAS in Ischemic Stroke, 46 and can promote atherosclerotic plaque formation. 47 The mechanism of KRAS in ischemic stroke and atherosclerosis is not clear.…”

Circulating MicroRNA Profiling Identifies Distinct MicroRNA Signatures in Acute Ischemic Stroke and Transient Ischemic Attack Patients

“…Hsa-miR-181a-5p is associated with inflammation, upregulated in response to TGFβ signaling [52], and has been identified as a critical regulatory miRNA in ischemic strokes [53]. Serum levels of the protein encoded by its gene targets ATG5 is presented as a biomarker for AIS patients [54], while another gene target, ATM is involved in neuroprotection in the initiation of protective mechanisms in ischemic preconditioning but promotes neuronal cell death following the ischemic insult [55].…”