Correlation and integration of circulating miRNA and peripheral whole blood gene expression profiles in patients with venous thromboembolism

Abstract

The main aim of this work was to evaluate differential expression and biological functions of circulating miRNA and whole peripheral blood (PB) genes in patients affected by venous thromboembolism (VTE) and in healthy subjects. Circulating miRNA sequences and PB expression profiles were obtained from GEO datasets. Ten miRNAs with the most significant differential expression rate (dif-miRNA) were subjected to miRbase to confirm their identity. Dif-miRNA targets were predicted by TargetScan and aligned with differentially expressed genes to obtain overlapping co-genes. Biological functions of co-genes were analyzed by Gene Ontology and KEGG analysis. Interaction network of dif-miRNAs, co-genes, and their downstream pathways were studied by analyzing protein–protein interaction (PPI) clusters (STRING) and determining the crucial hubs (Cytoscape). MiR-522-3p and miR-134 dif-miRNAs are involved in protein translation and apoptosis by regulating their respective co-genes in PB. Co-genes are present in nucleolus and extracellular exosomes and are involved in oxidative phosphorylation and ribosome/poly(A)-RNA organization. The predicted PPI network covered 107 clustered genes and 220 marginal joints, where ten hub genes participating in PPIs were found. All these hub genes were down-regulated in VTE patients. Our study identifies new miRNAs as potential biological markers and therapeutic targets for VTE.