Detection of circRNA Biomarker for Acute Myocardial Infarction Based on System Biological Analysis of RNA Expression

Abstract

Acute myocardial infarction (AMI) is myocardial necrosis caused by the persistent interruption of myocardial blood supply, which has high incidence rate and high mortality in middle-aged and elderly people in the worldwide. Biomarkers play an important role in the early diagnosis and treatment of AMI. Recently, more and more researches confirmed that circRNA may be a potential diagnostic biomarker and therapeutic target for cardiovascular diseases. In this paper, a series of biological analyses were performed to find new effective circRNA biomarkers for AMI. Firstly, the expression levels of circRNAs in blood samples of patients with AMI and those with mild coronary stenosis were compared to reveal circRNAs which were involved in AMI. Then, circRNAs which were significant expressed abnormally in the blood samples of patients with AMI were selected from those circRNAs. Next, a ceRNA network was constructed based on interactions of circRNA, miRNA and mRNA through biological analyses to detect crucial circRNA associated with AMI. Finally, one circRNA was selected as candidate biomarker for AMI. To validate effectivity and efficiency of the candidate biomarker, fluorescence in situ hybridization, hypoxia model of human cardiomyocytes, and knockdown and overexpression analyses were performed on candidate circRNA biomarker. In conclusion, experimental results demonstrated that the candidate circRNA was an effective biomarker for diagnosis and therapy of AMI.

The circRNA-miRNA/RBP regulatory network in myocardial infarction

“…ROC curve analyses showed that circRNA_104761 had high sensitivity and specificity. These findings suggested the possible diagnostic role of circRNA_10476 in AMI ( Yang et al, 2021 ).…”

“…Notably, circRNA_104761 was revealed to sponge microRNA-449 and microRNA-34a that is relevant to AMI ( Fan et al, 2013 ; Zhang M. et al, 2019 ). In a larger cohort, circRNA_104761 levels were the lowest in AMI patients and highest in healthy coronary artery volunteers, suggesting the abundant expression of circRNA_104761 in human blood ( Yang et al, 2021 ). ROC curve analyses showed that circRNA_104761 had high sensitivity and specificity.…”

“…Yang et al carried out a microarray analysis (GSE169594) in four AMI patients and four mild coronary artery stenosis patients by using whole blood samples Yang et al (2021). Three circRNAs (circRNA_068655, circRNA_104761, and circRNA_104765) were validated to be significantly downregulated (Yang et al, 2021). Notably, circRNA_104761 was revealed to sponge microRNA-449 and microRNA-34a that is relevant to AMI (Fan et al, 2013;Zhang M. et al, 2019).…”

Comprehensive Analysis of circRNA-miRNA-mRNA Regulatory Network and Novel Potential Biomarkers in Acute Myocardial Infarction

“…They are produced by reverse splicing of the precursor mRNA transcript, in which the upstream splicing receptor connects to the downstream splicing donor ( 6 ). As an effective sponge of miRNA, circRNA interacts with miRNA to regulate mRNA expression ( 7 ). A large number of studies have demonstrated that circRNA is involved in the development of a variety of cardiovascular diseases, including heart failure ( 8 ), atrial fibrillation ( 9 ), diabetic cardiomyopathy ( 10 ), dilated cardiomyopathy ( 11 ), acute myocardial infarction ( 12 ), and myocardial ischemia-reperfusion injury ( 13 ).…”

“…They are produced by reverse splicing of the precursor mRNA transcript, in which the upstream splicing receptor connects to the downstream splicing donor (6). As an effective sponge of miRNA, circRNA interacts with miRNA to regulate mRNA expression (7). A large number of studies have demonstrated that circRNA is involved in the development of a variety of cardiovascular diseases, including heart failure (8), atrial fibrillation (9), diabetic cardiomyopathy (10), dilated cardiomyopathy (11), acute Abbreviations: AMI, acute myocardial infarction; circRNA, circular RNA; lncRNA, long non-coding RNA; miRNA, microRNA; ncRNA, non-coding RNA; GEO, Gene Expression Omnibus; DERNA, Differential Expression RNA; PPI, protein-protein interaction; DEG, differentially expressed gene; PCI, percutaneous coronary intervention; CFs, cardiac fibroblasts; MRE, microRNA response element; RBP, RNA binding protein; ORF, open reading frames; GO, Gene Ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes; BP, biological process; CC, cellular component; MF, molecular function; ROC, receiver operating characteristic curve.…”