Oxidized low‐density lipoprotein accelerates the injury of endothelial cells via circ‐USP36/miR‐98‐5p/VCAM1 axis

Circular RNAs (circRNAs) are a group of RNAs featured by a covalently closed continuous loop structure. This study aimed to uncover the function and mechanism of circ‐ubiquitin specific peptidase 36 (USP36) in endothelial cells treated with oxidized low‐density lipoprotein (ox‐LDL). The levels of circ‐USP36, microRNA‐98‐5p (miR‐98‐5p) and vascular cell adhesion molecule 1 (VCAM1) were examined by a quantitative real‐time polymerase chain reaction (qRT‐PCR). The viability, apoptosis and inflammation were detected by (4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay, flow cytometry and enzyme‐linked immunosorbent assay (ELISA), respectively. Western blot assay was performed to detect the expression of apoptosis and proliferation‐related markers and VCAM1 protein level. The targets of circ‐USP36 and miR‐98‐5p were searched using starBase website, and dual‐luciferase reporter assay and RNA immunoprecipitation (RIP) assay were applied to validate the above predictions. Ox‐LDL exposure induced the upregulation of circ‐USP36 in HUVEC cells. Circ‐USP36 accelerated ox‐LDL‐induced apoptosis, inflammatory and viability inhibition of HUVEC cells. MiR‐98‐5p was a direct downstream gene of circ‐USP36. Circ‐USP36 promoted the injury of ox‐LDL‐induced HUVEC cells through targeting miR‐98‐5p. VCAM1 could bind to miR‐98‐5p, and the protective effects of miR‐98‐5p accumulation on ox‐LDL‐induced HUVEC cells were reversed by the transfection of VCAM1. VCAM1 was regulated by circ‐USP36/miR‐98‐5p signaling in HUVEC cells. Ox‐LDL promoted the apoptosis and inflammation but suppressed the viability of HUVEC cells through upregulating circ‐USP36, thus elevating the expression of VCAM1 via miR‐98‐5p.