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.

中文翻译：

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氧化低密度脂蛋白通过circ-USP36/miR-98-5p/VCAM1轴加速内皮细胞损伤

环状RNA（circRNA）是一组具有共价闭合连续环结构的RNA。本研究旨在揭示环泛素特异性肽酶 36 (USP36) 在氧化低密度脂蛋白 (ox-LDL) 处理的内皮细胞中的功能和机制。通过定量实时聚合酶链反应 (qRT-PCR) 检测 circ-USP36、microRNA-98-5p (miR-98-5p) 和血管细胞粘附分子 1 (VCAM1) 的水平。分别通过(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑(MTT)测定、流式细胞术和酶联免疫吸附测定(ELISA)检测活性、细胞凋亡和炎症。采用蛋白质印迹法检测细胞凋亡和增殖相关标志物的表达和VCAM1蛋白水平。使用starBase网站搜索circ-USP36和miR-98-5p的靶标，并应用双荧光素酶报告基因测定和RNA免疫沉淀（RIP）测定来验证上述预测。Ox-LDL 暴露诱导 HUVEC 细胞中 circ-USP36 的上调。Circ-USP36 加速了 ox-LDL 诱导的 HUVEC 细胞凋亡、炎症和活力抑制。MiR-98-5p 是 circ-USP36 的直接下游基因。Circ-USP36 通过靶向 miR-98-5p 促进 ox-LDL 诱导的 HUVEC 细胞损伤。VCAM1 可与 miR-98-5p 结合，转染 VCAM1 可逆转 miR-98-5p 积累对 ox-LDL 诱导的 HUVEC 细胞的保护作用。VCAM1 在 HUVEC 细胞中受 circ-USP36/miR-98-5p 信号传导的调节。