Construction of the ceRNA network in the progression of acute myocardial infarction.

Abstract

Acute myocardial infarction (AMI) is a common disease that induced by sudden occlusion of a coronary artery and myocardial necrosis, which causes a great medical burden worldwide. Noncoding RNAs, such as circRNA, lncRNA and miRNA, play crucial roles in the progression of cardiovascular diseases. However, the circRNA-miRNA-mRNA network in the occurrence and development of AMI needs further investigation. In this study, we downloaded three AMI datasets, including circRNA (GSE160717), miRNA (GSE24591), and mRNA (GSE66360) from GEO database. The differentially expressed candidates, and GO and KEGG functions were analyzed by RStudio, and subsequently import to PPI and Cytoscape to obtain the hub genes. By using the starbase target prediction database, we further screen the ceRNA network of circRNA-miRNA-mRNA based on the selected differentially expressed candidates. We found 46 differential expressed mRNAs, 65 miRNAs, and five circRNAs. GO functions and KEGG enrichment of the 46 mRNAs focused on immune response and functions, involving IL-17 signaling pathway, Toll-like receptor signaling pathway, cytokine-cytokine receptor interaction, TNF signaling pathway, chemokine signaling pathway, and NF-kappaB signaling pathway, which may aggravate the pathologies of AMI. PPI and Cytoscape analysis showed 10 hub genes, including TLR2, IL1B, CCL4, CCL3, CCR5, TREM1, CXCL2, NLRP3, CSF3, and CCL20. By using starbase and circinteractome databases, ceRNA network construction showed that circRNA_023461 and circRNA_400027 regulate several miRNA-mRNA axes in AMI. In summary, this study uncovered the circRNA-miRNA-mRNA network based on three AMI datasets. The differentially expressed genes, including CCL20, CCL4, CSF3, and IL1B, focus on immune functions and pathways. Furthermore, circRNA_023461 and circRNA_400027 regulate several miRNA-mRNA axes, exerting important roles in AMI progression. Our founding provides new insights into AMI and improve the therapeutic strategies for AMI.