Key result
Circ_0010283 knockdown suppresses ox-LDL-induced VSMC proliferation and migration via the miR-133a-3p/PAPPA pathway.
Why the study?
The role of circ_0010283 in ox-LDL-induced dysfunction of vascular smooth muscle cells and its underlying mechanism in atherosclerosis was unclear.
circ_0010283 promotes ox-LDL-induced dysfunction of human vascular smooth muscle cells via the miR-133a-3p/PAPPA axis, highlighting a potential therapeutic target for atherosclerosis.
Answers are grounded in this paper and cite their sources.
circ_0010283 may regulate VSMC proliferation in atherosclerosis models; leaves open therapeutic relevance pending in vivo studies.
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.
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Feng et al. (2020) studied Atherosclerosis (n=72). circ_0010283 knockdown vs. Negative control (si-NC) was evaluated on Cell proliferation, migration, invasion, and apoptosis (p=<0.05). Knockdown of circ_0010283 suppressed ox-LDL-induced proliferation, migration, and invasion in human vascular smooth muscle cells by modulating the miR-133a-3p/PAPPA pathway.
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