Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Cardiol. Jan 26, 2025; 17(1): 102147
Published online Jan 26, 2025. doi: 10.4330/wjc.v17.i1.102147
Profiling and bioinformatics analyses of circular RNAs in myocardial ischemia/reperfusion injury model in mice
Jiao-Ni Wang, Ying-Ying Zhou, Yong-Wei Yu, Jun Chen
Jiao-Ni Wang, Department of Diagnostic Ultrasound and Echocardiography, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310002, Zhejiang Province, China
Ying-Ying Zhou, Department of Endocrinology, The Second Affliated and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
Yong-Wei Yu, Department of Critical Care Medicine, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang Province, China
Jun Chen, Cardiac Care Unit, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
Co-first authors: Jiao-Ni Wang and Ying-Ying Zhou.
Co-corresponding authors: Yong-Wei Yu and Jun Chen.
Author contributions: Wang JN completed database processing, data export and manuscript writing; Zhou YY was responsible for the final compilation of pictures and tables; Yu YW and Chen J guided the idea of the manuscript; all of the authors read and approved the final version of the manuscript to be published.
Supported by Zhejiang Provincial Natural Science Foundation of China, No. LQ23H020004; The Medical and Health Research Project of Zhejiang province, No. 2024KY983; Basic Medical Health Technology Project of Wenzhou Science and Technology Bureau, No. Y20210818 and No. Y20210140.
Institutional review board statement: Our work was approved by the Ethics Committee of Wenzhou Medical University.
Institutional animal care and use committee statement: All animal operations approved by the Animal Care and Use Committee at the Wenzhou Medical University (No. wydw2024-0565).
Conflict-of-interest statement: The authors declare that they have no competing interests.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: Different mRNA, circRNA, lncRNA and microRNA results obtained by sequencing were stored in GSE240842. If you need the R code for specific analysis, you can contact the corresponding author to obtain it.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yong-Wei Yu, PhD, Assistant Professor, Department of Critical Care Medicine, The First Affiliated Hospital of Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou 310000, Zhejiang Province, China. yuyongwei@zju.edu.cn
Received: October 9, 2024
Revised: November 23, 2024
Accepted: December 19, 2024
Published online: January 26, 2025
Processing time: 103 Days and 14.8 Hours
Abstract
BACKGROUND

Myocardial ischemia/reperfusion (I/R) injury, which is associated with high morbidity and mortality, is a main cause of unexpected myocardial injury after acute myocardial infarction. However, the underlying mechanism remains unclear. Circular RNAs (circRNAs), which are formed from protein-coding genes, can sequester microRNAs or proteins, modulate transcription and interfere with splicing. Authoritative studies suggest that circRNAs may play an important role in myocardial I/R injury.

AIM

To explore the role and mechanism of circRNAs in myocardial I/R injury.

METHODS

We constructed a myocardial I/R injury model using ligation of the left anterior descending coronary artery, and evaluated the success of the validated model using triphenyltetrazolium chloride and hematoxylin-eosin staining. Then, left ventricular samples from different groups were selected for mRNA-sequence, and differential gene screening was performed on the obtained results. The differentially obtained mRNAs were divided into up-regulated and down-regulated according to their expression levels, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis were performed, respectively. Then, the obtained circRNA and microRNA (miRNA) were paired for analysis, and the binding sites of miRNA and mRNA were virtual screened. Finally, the obtained circRNA, miRNA and mRNA were constructed by ceRNA mutual most useful network.

RESULTS

We used an RNA sequencing array to investigate the expression signatures of circRNAs in myocardial I/R injury using three samples from the I/R group and three samples from the sham group. A total of 142 upregulated and 121 downregulated circRNAs were found to be differentially expressed (fold change ≥ 2, P < 0.05). GO and KEGG functional analyses of these circRNAs were performed. GO analysis revealed that these circRNAs were involved mainly in cellular and intracellular processes. KEGG analysis demonstrated that 6 of the top 20 pathways were correlated with cell apoptosis. Furthermore, a circRNA-miRNA coexpression network and ceRNA network based on these genes were constructed, revealing that mmu-circ-0001452, mmu-circ-0001637, and mmu-circ-0000870 might be key regulators of myocardial I/R injury.

CONCLUSION

This research provides new insights into the mechanism of myocardial I/R, which mmu-circ-0001452, mmu-circ-0001637, and mmu-circ-0000870 are expected to be new therapeutic targets for myocardial I/R injury.

Keywords: Rna-sequencing; Circular RNA; MicroRNA; CeRNA; Myocardial ischemia/reperfusion; Bioinformatics analyses

Core Tip: The circular RNA-microRNA coexpression network and ceRNA network revealing that mmu-circ-0001452, mmu-circ-0001637, and mmu-circ-0000870 might be key regulators of myocardial ischemia/reperfusion (I/R) injury. This research provides new insights into the mechanism of myocardial I/R and identifies a new target for the prevention and treatment of myocardial I/R injury.