Circ_USP36/miR-182-5p/KLF5 axis regulates the ox-LDL-induced injury in human umbilical vein smooth muscle cells.

Atherogenesis is a chronic inflammatory process, closely related to high morbidity and mortality. Circular RNAs (circRNAs) were reported to function in atherosclerosis. However, the functional impact of circRNA ubiquitin-specific Protease 36 (circ_USP36) on atherosclerosis and the possible mechanism are still unclear. Serum specimens were collected from atherosclerosis patients and healthy volunteers. Human umbilical vein smooth muscle cells (HUVSMCs) exposed with 25 μg/mL oxidized low-density lipoprotein (ox-LDL) were utilized to simulate atherosclerosis. Expression of circ_USP36, microRNA (miR)-182-5p and Kruppel-like factor 5 (KLF5) was determined via quantitative real-time polymerase chain reaction or western blot assay. Cell viability and apoptosis were evaluated by Cell Counting Kit-8 and flow cytometry. Cell metastasis, including migration and invasion, was assessed via Transwell assay. Biomarker protein was analyzed by western blot. The relationship among circ_USP36, miR-182-5p and KLF5 was confirmed by dual-luciferase reporter and RNA pull-down assays. Circ_USP36 and KLF5 were up-regulated, while miR-182-5p was down-regulated in atherosclerosis patients and ox-LDL-induced HUVSMCs. Circ_USP36 knockdown inhibited proliferation and metastasis of ox-LDL-induced HUVSMCs by up-regulating miR-182-5p. MiR-182-5p targeted KLF5, and ameliorated ox-LDL-mediated injury of HUVSMCs. Circ_USP36 knockdown down-regulated KLF5 expression by sponging miR-182-5p. Knockdown of circ_USP36 alleviated ox-LDL-mediated injury of HUVSMCs by modulating miR-182-5p/KLF5 axis, potentially providing a treatment target for atherosclerosis. AJTR