Oxygenized Low-Density Lipoprotein-Induced ASMC Dysregulation Depends on circ_0000345-Mediated Regulatory Mechanism

抄録

Aims: Vascular smooth muscle cells are key participants in atherosclerosis. Circular RNA hsa_circ_0000345 (circ_0000345) and miR-647 are related to oxygenized low-density lipoprotein (ox-LDL)-induced arterial smooth muscle cell (ASMC) dysregulation. However, the relationship between circ_0000345 and miR-647 in ox-LDL-induced ASMC dysregulation is unclear.

Methods: Relative levels of circ_0000345, miR-647, and PAP-associated domain containing 5 (PAPD5) mRNA in AS patient's serum and ox-LDL-induced ASMCs were detected via RT-qPCR. Gain-of-function experiments were utilized to analyze the effects of circ_0000345 upregulation on ox-LDL-induced cell proliferation, migration, invasion, and inflammatory response in ASMCs. The relationship between circ_0000345 or PAPD5 and miR-647 was validated by dual-luciferase reporter and RNA immunoprecipitation assays.

Results: Circ_0000345 and PAPD5 were lowly expressed in AS patient's serum and ox-LDL-induced ASMCs, while miR-647 expression had an opposing trend. Mechanistically, circ_0000345 was verified as a miR-647 sponge, and miR-647 overexpression impaired the inhibitory effects of circ_0000345 upregulation on ox-LDL-induced ASMC proliferation, migration, invasion, and inflammatory response. Further experiments demonstrated that PAPD5 was a miR-647 target, and circ_0000345 adsorbed miR-647 to mediate PAPD5 expression. Also, PAPD5 inhibition relieved miR-647 silencing-mediated suppression on ox-LDL-induced ASMC proliferation, migration, invasion, and inflammatory response.

Conclusions: Circ_0000345 elevated PAPD5 expression via acting as a miR-647 sponge, resulting in alleviating ox-LDL-induced ASMC dysregulation. The study highlighted the critical role of circ_0000345 in AS.