Abstract
Coronary heart disease (CHD) is a prevalent global cause of death. Research suggests that circular RNAs (circRNAs) play a role in the development of CHD. In this study, we investigated the expression of hsa_circRNA_0000284 in peripheral blood leukocytes (PBLs) obtained from a cohort of 94 CHD patients aged over 50 years, as well as 126 age-matched healthy controls (HC). An in vitro inflammatory and oxidative injury cell model that simulates CHD was used to evaluate changes in hsa_ circRNA _0000284 under stress. CRISPR/Cas9 technology was used to evaluate changes in hsa_circRNA_0000284 expression. An hsa_ circRNA_0000284 overexpression and silencing cell model was used to analyze the biological functions of hsa_circRNA_0000284. Bioinformatics, qRT-PCR, viral transfection technology, and luciferase assays were used to evaluate the potential hsa_circRNA_0000284/miRNA-338-3p/ETS1 axis. Western blotting analysis was performed to detect protein expression. Herein, PBLs from CHD patients exhibited downregulation of hsa_circRNA_0000284 expression. Exposure to oxidative stress and inflammation can induce damage to human umbilical endothelial cells, resulting in the downregulation of hsa_circRNA_0000284 expression. The expression of hsa_circRNA_0000284 in EA-hy926 cells was significantly reduced after the AluSq2 element of hsa_circRNA_0000284 had been knocked out. The expression of hsa_circRNA_0000284 affected proliferation, cycle distribution, aging, and apoptosis in EA-hy926 cells. Consistent with the results of cell transfection experiments and luciferase assays, Western blotting showed that hsa_circRNA_0000284 plays a role in the regulation of hsa-miRNA-338-3p expression. Subsequently, hsa-miRNA-338-3p was found to be involved in the regulation of ETS1 expression.
Communicated by Ramaswamy H. Sarma
Acknowledgements
We extend our sincere appreciation to the patients and staff members at The Second Affiliated Hospital of Guangxi Medical University and the Departments of Cardiology of the People’s Hospital of Guangxi Zhuang Autonomous Region for their invaluable support and cooperation throughout the sample collection process.
Disclosure statement
No potential conflict of interest was reported by the authors.
Data availability statement
The datasets utilized and analyzed in this study are not publicly accessible in accordance with the confidentiality principles of the funding source. However, interested parties may request access to the datasets from the corresponding author.
Ethics approval
The present study received ethical approval from the Research and Ethics Committee of Guangxi Medical University (No. 2019-SB-060) and was conducted in strict adherence to the ethical principles outlined in the Helsinki Declaration. Written informed consent was obtained from all participants, including the selected patients and controls.
Authors’s contributions
PhongSon Dinh: analyzed and interpreted data, and drafted the manuscript, ChauMyThanh Tran: validated data and results. ThiPhuongHoai Dinh:Writning and proof reading, Awais Ali: interpreted data, ShangLing Pan: designed the study and revised the manuscript. All authors read and approved the final manuscript,