Identification of Regulatory circRNAs Involved in the Pathogenesis of Acute Myocardial Infarction

Cuimei Zhao; Jingjing Liu; Wen Ge; Zhi Li; Mengwei Lv; Yipeng Feng; Xuebo Liu; Ban Liu; Yangyang Zhang

doi:10.3389/fgene.2020.626492

Identification of Regulatory circRNAs Involved in the Pathogenesis of Acute Myocardial Infarction

Front Genet. 2021 Feb 3:11:626492. doi: 10.3389/fgene.2020.626492. eCollection 2020.

Authors

Cuimei Zhao¹, Jingjing Liu², Wen Ge³, Zhi Li⁴, Mengwei Lv^{5

6}, Yipeng Feng⁷, Xuebo Liu¹, Ban Liu⁸, Yangyang Zhang^{5

6}

Affiliations

¹ Department of Cardiology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
² Department of Cardiology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, China.
³ Department of Cardiothoracic Surgery, Shuguang Hospital Affiliated to Shanghai University of TCM, Shanghai, China.
⁴ Department of Cardiovascular Surgery, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
⁵ Shanghai East Hospital of Clinical Medical College, Nanjing Medical University, Shanghai, China.
⁶ Department of Cardiovascular Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
⁷ The First Clinical Medical College, Nanjing Medical University, Nanjing, China.
⁸ Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

Abstract

Background: Acute myocardial infarction (AMI) has high morbidity and mortality worldwide. However, the pathogenesis of AMI is still unclear, and the impact of circular RNAs (circRNAs) on AMI has rarely been recognized and needs to be explored.

Materials and methods: The circRNA array was applied to investigate the expression level of circRNAs in the blood samples of coronary arteries of three AMI patients and three normal persons. Principal component analysis (PCA) and unsupervised clustering analysis were performed to reveal the distinguished expression patterns of circRNAs. The miRNA expression profiles of AMI patients were identified from a public dataset from the Gene Expression Omnibus (GEO) database (GSE31568). The miRNA binding sites on the circRNAs were predicted by miRanda. The miRNA enrichment analysis and annotation tool were used to explore the pathways that the dysregulated circRNAs may participate in.

Results: In total, 142 differentially expressed circRNAs, including 89 upregulated and 53 downregulated in AMI samples, were identified by the differential expression analysis. AMI patients had quite different circRNA expression profiles to those of normal controls. Functional characterization revealed that circRNAs that had the potential to regulate miRNAs were mainly involved in seven pathways, such as the Runt-related transcription factor-1 (RUNX1) expression and activity-related pathway. Specifically, hsa_circRNA_001654, hsa_circRNA_091761, hsa_circRNA_405624, and hsa_circRNA_406698 were predicted to sponge four miRNAs including hsa-miR-491-3p, hsa-miR-646, hsa-miR-603, and hsa-miR-922, thereby regulating RUNX1 expression or activity.

Conclusion: We identified dysregulated blood circRNAs in the coronary arteries of AMI patients and predicted that four upregulated circRNAs were involved in the regulation of RUNX1 expression or activity through sponging four miRNAs.

Keywords: acute myocardial infarction; circRNA; functional characterization; miRNA; runt-related transcription factor-1.