Circular RNA circ_0124644 exacerbates the ox-LDL-induced endothelial injury in human vascular endothelial cells through regulating PAPP-A by acting as a sponge of miR-149-5p

摘要

The modulatory roles of numerous circular RNAs (circRNAs) have been exposited in atherosclerosis (AS). Our study paid attention to the function of circRNA_ 0124644 (circ_0124644) in AS development, as well as its functional mechanism. The AS cell model was established by the treatment of oxidized low-density lipoprotein (ox-LDL) to human vascular endothelial cells (HUVECs). Cell proliferation and cycle were severally measured by Cell Counting Kit-8 (CCK-8) and cell cycle detection kit. The examination of apoptosis rate was executed through flow cytometry. Western blot was exploited for detecting the associated proteins. The expression levels of circ_0124644 and microRNA-149-5p (miR-149-5p) and pregnancy-associated plasma protein-A (PAPP-A) were assayed using quantitative real-time polymerase chain reaction. The combination of targets was validated via the dual-luciferase reporter assay, RNA immunoprecipitation (RIP), and RNA pull-down assay. Clonal capacity was analyzed using colony formation assay. Ox-LDL restrained HUVECs proliferation and cycle, but facilitated apoptosis. Circ_0124644 expression was increased, while miR-149-5p was downregulated in ox-LDL-treated HUVECs. Besides, circ_0124644 served as a molecular sponge of miR-149-5p and intensified the ox-LDL-induced HUVECs injury by sponging miR-149-5p. PAPP-A was a target of miR-149-5p and miR-149-5p could mitigate the HUVECs injury caused by ox-LDL through inhibiting PAPP-A. Moreover, PAPP-A was positively regulated by circ_0124644 via the miR-149-5p. In this report, we concluded the promoted role of circ_0124644 in the ox-LDL-induced endothelial injury of HUVECs via the miR-149-5p/PAPP-A axis with an emphasis on its diagnostic and therapeutic values in AS.