Circular RNA circ_0029589 promotes ox-LDL-induced endothelial cell injury through regulating RAB22A by serving as a sponge of miR-1197

Article type: Research Article

Authors: He, Dequan^a | Li, Zhiliang^{a; b; *} | Chen, Youquan^c | Huang, Ming^c

Affiliations: [a] Department of Cardiology, Heart Center, Zhujiang Hospital of Southern Medical University, Guangzhou, China | [b] Department of Cardiology, Heart Center, South China hospital, Health Science Center, Shenzhen University, Shenzhen, China | [c] Department of Cardiology, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China

Correspondence: [*] Corresponding author: Zhiliang Li, Department of Cardiology, Zhujiang Hospital of Southern Medical University, Guangzhou 510000, China. Department of Cardiology, South China hospital, Health Science Center, Shenzhen University, No.1 Fuxin Road, Longgang District, Shenzhen 518116, China. Tel.: +86 0755 89698999; E-mail: [email protected].

Abstract: BACKGROUND:Dysfunction of endothelial cells is now considered a vital contributor to the pathogenesis of atherosclerosis (AS). Moreover, circular RNA (circRNA) circ_0029589 has been found to be involved in the regulation of oxidized low-density lipoprotein (ox-LDL)-induced endothelial cell damage. Nevertheless, its molecular mechanism in ox-LDL-triggered endothelial cell injury is poorly defined. METHODS:Human umbilical vein endothelial cells (HUVECs) treated with ox-LDL were applied as cell models of AS. Circ_0029589, microRNA-1197 (miR-1197), and Ras-related protein Rab-22A (RAB22A) expression were detected using real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation, apoptosis, angiogenesis, and invasion were detected using 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT), 5-ethynyl-2’-deoxyuridine (EdU), flow cytometry, tube formation, and transwell assays. Western blot analysis of Cleaved-caspase-3, B-cell lymphoma-2 related X protein (Bax), and RAB22A. IL-6, IL-1β, and Tumor necrosis factor α (TNF-α) levels were gauged using ELISA kits. Superoxide Dismutase (SOD) activity and Malondiahyde (MDA) level were assessed using special kits. Bioinformatics software predicted the binding between miR-1197 and circ_0029589 or RAB22A, which was proved using dual-luciferase reporter and RNA pull-down assays. RESULTS:Circ_0029589 and RAB22A expression were strengthened, and miR-1197 was reduced in ox-LDL-treated HUVECs. Importantly, circ_0029589 silencing ameliorated ox-LDL-triggered HUVEC damage via promoting cell proliferation, tube formation ability, invasion, and repressing cell apoptosis, inflammation, and oxidative stress. Mechanical analysis suggested that circ_0029589 might affect RAB22A content through sponging miR-1197. CONCLUSION:Circ_0090231 might protect against ox-LDL-mediated HUVEC injury via the miR-1197/RAB22A axis, which provides a therapeutic strategy for endothelial cell damage of AS.

Keywords: Circ_0029589, miR-1197, RAB22A, ox-LDL, atherosclerosis

DOI: 10.3233/CH-221657

Journal: Clinical Hemorheology and Microcirculation, vol. 83, no. 4, pp. 359-376, 2023