Hsa-circ_0010283 Regulates Oxidized Low-Density Lipoprotein-Induced Proliferation and Migration of Vascular Smooth Muscle Cells by Targeting the miR-133a-3p/Pregnancy-Associated Plasma Protein A Axis

Abstract

Background: The dysfunction of vascular smooth muscle cells (VSMCs) contributes to the development of atherosclerosis. This study aimed to investigate the role of circular RNA-0010283 (circ_0010283) in oxidized low-density lipoprotein (ox-LDL)-treated VSMCs and the associated action mechanism. Methods and Results: The expression of circ_0010283 was investigated using quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was monitored by using a 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Cell apoptosis was detected by using flow cytometry assay. A transwell assay was performed to observe migration and invasion, and a scratch assay was implemented to test migration. The expression of proliferation, apoptosis and migration/invasion-related proteins was measured by using a western blot. The targeted relationship was predicted by using a bioinformatics tool (Starbase) and verified by using a dual-luciferase reporter assay, a RNA immunoprecipitation (RIP) assay and a RNA pull-down assay. circ_0010283 was highly expressed in serum samples from atherosclerosis patients and ox-LDL-treated human VSMCs (HVSMCs). circ_0010283 knockdown suppressed ox-LDL-induced proliferation, migration and invasion in HVSMCs. MicroRNA-133a-3p (miR-133a-3p) was confirmed as a target of circ_0010283, and miR-133a-3p deficiency reversed the effects of circ_0010283 knockdown. Moreover, pregnancy-associated plasma protein A (PAPPA) was targeted by miR-133a-3p, and PAPPA overexpression reversed the effects of miR-133a-3p restoration. Interestingly, circ_0010283 could regulate PAPPA expression by mediating miR-133a-3p. Conclusions: circ_0010283 participated in ox-LDL-induced dysfunctions of HVSMCs by modulating the miR-133a-3p/PAPPA pathway, suggesting that circ_0010283 might be associated with atherosclerosis pathogenesis.