血管平滑肌
竞争性内源性RNA
化学
细胞生物学
癌症研究
平滑肌
内科学
下调和上调
生物
医学
生物化学
基因
长非编码RNA
作者
Huaiyu Peng,Shunfan Liu,Yang Li,Chengyang Wang,Yang Zhong
出处
期刊:Journal of Cardiovascular Pharmacology
[Ovid Technologies (Wolters Kluwer)]
日期:2022-04-01
卷期号:79 (4): 512-522
被引量:6
标识
DOI:10.1097/fjc.0000000000001204
摘要
Vascular smooth muscle cells (VSMCs) play critical roles in the progression of atherosclerosis. Circular RNA (circRNA) ubiquitin protein ligase E3 component n-recognin 4 (circUBR4) has been shown to regulate VSMC migration and proliferation. In this study, we sought to identify the mechanism in the regulation of circUBR4. CircUBR4, microRNA (miR)-491-5p, and Neuropilin-2 (NRP2) were quantified by quantitative real-time polymerase chain reaction (PCR) and western blot. Cell proliferation was evaluated by Cell Counting Kit-8 and 5-Ethynyl-2'-Deoxyuridine assays. Cell migration was examined by wound-healing and transwell invasion assays. The direct relationship between miR-491-5p and circUBR4 or NRP2 was validated by dual-luciferase reporter and RNA immunoprecipitation assays. Our data indicated that in VSMCs, ox-LDL induced circUBR4 expression. Silencing endogenous circUBR4 attenuated VSMC proliferation and migration induced by ox-LDL. Mechanistically, circUBR4 targeted miR-491-5p by pairing to miR-491-5p. Moreover, miR-491-5p was identified as a downstream mediator of circUBR4 function in ox-LDL-treated VSMCs. NRP2 was a direct target of miR-491-5p, and circUBR4 acted as a competing endogenous RNA for miR-491-5p to regulate NRP2 expression. In addition, NRP2 was a functionally downstream effector of miR-491-5p in regulating ox-LDL-evoked VSMC proliferation and migration. Our findings identify a new competing endogenous RNA network, the circUBR4/miR-491-5p/NRP2 axis, for the regulation of circUBR4 in VSMC migration and proliferation.
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