circRNA, a novel diagnostic biomarker for coronary heart disease

Abstract

Objective: This study aimed to identify the potential diagnostic biomarkers of coronary heart disease (CHD) from exosome-derived circRNA.

Methods: The microarray data of circRNA derived from the exosomes of patients with CHD and mRNA in acute myocardial infarction was retrieved from exoRBase website and GEO database (GSE61144), respectively, to identify the differentially expressed genes (DEGs). Our findings detected the differentially expressed circRNAs and mRNAs and predicted their correlation with microRNAs using the microRNA target prediction website, thus ascertaining the corresponding circ-microRNA and micro-mRNAs. Then, we performed systematic Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis on the differentially expressed mRNA. Protein-Protein Interactions (PPI) of these DEGs were examined using STRING. The receiver operator characteristic (ROC) curve was used to validate the diagnostic efficacy of circRNA in patients with CHD. Finally, the RNAs identified in this study were verified by quantitative real-time polymerase chain reaction (qRT-PCR).

Results: A total of 85 differentially expressed circRNAs (4 up-regulated and 81 down-regulated) were identified by screening the circRNAs in exosome of CHD patients. Based on the prediction data of circRNA, mRNA, and the corresponding microRNA, a ceRNA network was constructed, including 7 circRNA nodes, 5 microRNA nodes, and 2 mRNA nodes. Finally, validated by qRT-PCR testing, we found circRNA0001785, circRNA0000973, circRNA0001741, and circRNA0003922 to be the promising candidate for the effective prediction of CHD. These potential diagnostic markers can provide insight for further research on the occurrence of CHD or even acute coronary syndrome (ACS).

Keywords: ceRNA network; coronary heart disease; diagnostic marker; differentially expressed genes; plasma exosome.