Prediction of circulating immune circRNA-miRNA-mRNA axis in patients with ischemic stroke
Objective:To investigate the circulating immune circRNA-miRNA-mRNA axis in patients with ische-mic stroke(IS),and to find molecular targets forthe treatment of IS.Methods:The GSE16561,GSE195442 datasets were retrieved from the GEO database,using the R software or the GEO2R tool to find the differentially expressed genes,circRNAs between the blood of ischemic stroke patients and normal controls.A protein-protein interaction(PPI)net-work was constructed through the STRING database,visualized with Cytoscape 3.9.1,and genes with high scores were selected using the Betweenness Centrality in CytoNCA.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Ge-nomes(KEGG)pathway enrichment analysis were performed on the top 15 differential genes with high scores.Thereaft-er,the miRNA-mRNA regulatory network was constructed by predicting the target miRNAs according to the mirTargets 2.0 database.The differentially expressed circRNAs in IS patients were selected using the GEO2R tool,Combined with literature selected significant differences circRNAs and what has been validated by PCR,the circRNA-miRNA regula-tory network was constructed using Circular RNA Interactome.The intersection of the two regulatory networks predicted the possible regulatory networks in the IS,and further constructed the immune-related circRNA-miRNA-mRNA ax-is,Validation of the miRNAs in the immune-related circRNA-miRNA-mRNA axis using the GSE117064 dataset.Results:This study identified many transcription factors,genes including CD247,IL2RB,STAT1,and miRNAs inclu-ding hsa-miR-892a,hsa-miR-938,hsa-miR-338-3p,and predicted seven possible immune-related cir-cRNA-miRNA-mRNA axes,for example hsa_circ_0112036-hsa-miR-892a-CD247,hsa_circ_0112036-hsa-miR-892a-IL2RB,hsa_circ_0093708-hsa-miR-1248-STAT1.Conclusion:The hsa_circ_0112036 may serve as a molecular sponge of hsa-miR-892a,hsa-miR-938,hsa-miR-1276,hsa-miR-1208,and hsa-miR-338-3p to regulate the progression of IS.Regulating IS progression as hsa_circ_0093708 may act as a molecular sponge for hsa-miR-1248.