Circ-CHFR modulates the proliferation, migration, and invasion of ox-LDL-induced human aorta vascular smooth muscle cells through the miR-214-3p/PAPPA axis

Article type: Research Article

Authors: Lu, Qianqian^{a; 1} | Li, Ying^{b; 1} | Lou, Jiaping^c | Li, Pingzhen^a | Gu, Yi^d | Wang, Xianghai^{e; *}

Affiliations: [a] Third Department of Cardiology, First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi City, Xinjiang, China | [b] Department of Emergency, First Teaching Hospital of Tianjin University of TCM, Tianjin, China | [c] Department of Cardiology, Yuquan Hospital of Tsinghua University, Beijing, China | [d] Department of Cardiology, Nanjing Jiangbei People’s Hospital Affiliated to Nantong University, Nanjing City, Jiangsu Province, China | [e] Department of Cardiology, Yijishan Hospital of Wan Nan Medical College, Wuhu City, Anhui Province, China

Correspondence: [*] Corresponding author: Xianghai Wang, Department of Cardiology, Yijishan Hospital of Wan Nan Medical College, No. 2, Zheshan West Road, Wuhu241001, Anhui Province, China. Tel.: +86 055 35739550; E-mail: doctor6901@sina.com.

Note: [1] These authors contributed equally to this work.

Abstract: Circular RNAs (circRNAs) are associated with the pathogenesis of human diseases, including atherosclerosis. Here, we undertook to investigate the biological role and mechanism of circRNA E3 ubiquitin-protein ligase (circ-CHFR) in atherosclerosis. The expression levels of circ-CHFR, miR-214-3p, and pregnancy-associated plasma protein A (PAPPA) were measured by real-time quantitative polymerase chain reaction (RT-qPCR) and western blot in human aorta vascular smooth muscle cells (HA-VSMCs) exposed to oxidized low-density lipoprotein (ox-LDL). Cell proliferation, migration, and invasion capabilities were assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium bromide (MTT), and transwell assays, respectively. The relationship between miR-214-3p and circ-CHFR or PAPPA was confirmed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Our data showed that circ-CHFR was upregulated in HA-VSMCs after stimulation with ox-LDL. Downregulation of circ-CHFR inhibited the proliferation, migration, and invasion of HA-VSMCs exposed to ox-LDL. Mechanistically, circ-CHFR acted as a miR-214-3p sponge, and miR-214-3p was a molecular mediator of circ-CHFR regulation in ox-LDL-stimulated HA-VSMCs. PAPPA was a miR-214-3p target, and circ-CHFR regulated the expression of PAPPA by sponging miR-214-3p. Moreover, overexpression of miR-214-3p repressed the proliferation, migration, and invasion of ox-LDL-induced HA-VSMCs by decreasing PAPPA expression. Our findings suggest that the circ-CHFR/miR-214-3p/PAPPA axis regulates ox-LDL-induced proliferation, migration, and invasion in HA-VSMCs.

Keywords: CircRNA, circ-CHFR, miR-214-3p, PAPPA, ox-LDL, HA-VSMCs

DOI: 10.3233/CH-211288

Journal: Clinical Hemorheology and Microcirculation, vol. 80, no. 4, pp. 399-412, 2022