Circ_0090231 knockdown protects vascular smooth muscle cells from ox-LDL-induced proliferation, migration and invasion via miR-942-5p/PPM1B axis during atherosclerosis

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Abstract
Atherosclerosis (AS) is a dominant pathological basis of cardiovascular disease. Circular RNAs (circRNAs) have been proposed to have crucial functions in regulating pathological progressions of AS. Hence, the aim of this study was to investigate the potential function of circ_0090231 in AS progression. Oxidized low densitylipoprotein (ox-LDL)-challenged vascular smooth muscle cells (VSMCs) were used for in vitro functional analysis. Levels of genes and proteins were measured by qRT-PCR and Western blot. The proliferation, migration and invasion were assessed using cell counting kit-8, 5-ethynyl-2’-deoxyuridine, and transwell assays. The interaction between miR-942-5p and circ_0090231 or PPM1B (Protein Phosphatase, Mg2+/Mn2+ Dependent 1B) was evaluated by dual-luciferase reporter and pull-down assays. Circ_0090231 is a stable circRNA, and was increased in the serum of AS patients and ox-LDL-challenged VSMCs. Functionally, silencing of circ_0090231 could reverse ox-LDL-induced proliferation, migration and invasion in VSMCs. Mechanistically, circ_0090231 directly targeted miR-942-5p, and PPM1B was a target of miR-942-5p. Besides, circ_0090231 sequestered miR-942-5p to release PPM1B expression, suggesting the circ_0090231/miR-942-5p/PPM1B axis. Further rescue experiments showed that miR-942-5p inhibition or ectopic overexpression of PPM1B dramatically attenuated the suppressing influences of circ_0090231 knockdown on VSMC proliferative, migratory and invasive abilities under ox-LDL treatment. Silencing of circ_0090231 could reverse ox-LDL-induced proliferation, migration and invasion in VSMCs via miR-942-5p/PPM1B axis, providing a theoretical basis for elucidating the mechanism of AS process.

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