Abstract
Atherosclerosis is a fatal disorder that is fundamental to various cardiovascular diseases and severely threatens people's health worldwide. Several studies have demonstrated the role of circular RNAs (circRNAs) in the pathogenesis of atherosclerosis. circUSP36 acts as a key modulator in the progression of atherosclerosis, but the molecular mechanism underlying this role is as yet unclear. This study aimed to elucidate the mechanism by which circUSP36 exerts its function in an in vitro cell model of endothelial cell dysfunction, which is one of pathological features of atherosclerosis. The circRNA traits of circUSP36 were confirmed, and we observed high expression of circUSP36 in endothelial cells exposed to oxidized low-density lipoprotein (ox-LDL). Functional assays revealed that overexpression of circUSP36 suppressed proliferation and migration of ox-LDL-treated endothelial cells. In terms of its mechanism, circUSP36 adsorbed miR-637 by acting as an miRNA sponge. Moreover, enhanced expression of miR-637 abated the impact of circUSP36 on ox-LDL-treated endothelial cell dysregulation. Subsequently, the targeting relationship between miR-637 and WNT4 was predicted using bioinformatics tools and was confirmed via luciferase reporter and RNA pull-down assays. Notably, depletion of WNT4 rescued circUSP36-mediated inhibition of endothelial cell proliferation and migration. In conclusion, circUSP36 regulated WNT4 to aggravate endothelial cell injury caused by ox-LDL by competitively binding to miR-637; this finding indicates circUSP36 to be a promising biomarker for the diagnosis and therapy of atherosclerosis.