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circ_0003204通过调控miR-942-5p/HDAC9轴调节氧化型低密度脂蛋白诱导的血管内皮细胞的细胞生长、氧化应激和炎症反应。

circ_0003204 Regulates Cell Growth, Oxidative Stress, and Inflammation in ox-LDL-Induced Vascular Endothelial Cells via Regulating miR-942-5p/HDAC9 Axis.

作者信息

Wan Huan, You Ting, Luo Wei

机构信息

Department of Cardiology, The First Affiliated Hospital of University of South China, Hengyang, China.

Department of Emergency, The First Affiliated Hospital of University of South China, Hengyang, China.

出版信息

Front Cardiovasc Med. 2021 Apr 1;8:646832. doi: 10.3389/fcvm.2021.646832. eCollection 2021.

Abstract

Atherosclerosis (AS) is a typical inflammatory vascular disease. Many reports corroborated that circular RNAs (circRNAs) is involved in AS progression. However, the potential function and possible mechanism of circ_0003204 in AS progression remain indistinct. Expression level analysis was performed using qRT-PCR and western blot. Cell viability and apoptosis were determined using Cell Counting Kit-8 (CCK-8), flow cytometry, and western blot assays. The status of oxidative stress and inflammation was determined via commercial detection kits and ELISA assay, respectively. The binding relationship was verified via dual-luciferase reporter and RNA immunoprecipitation assays. ox-LDL increased circ_0003204 and HDAC9 levels and decreased miR-942-5p level. Silencing of circ_0003204 enhanced cell viability and inhibited cell apoptosis, oxidative stress and inflammation in ox-LDL-disposed HUVECs. In addition, circ_0003204 targeted miR-942-5p to regulate ox-LDL-resulted HUVECs injury. Also, miR-942-5p affected ox-LDL-triggered HUVECs injury by targeting HDAC9. Furthermore, circ_0003204 elevated HDAC9 expression via decoying miR-942-5p. circ_0003204 aggravated ox-LDL-induced HUVECs damage via modulating miR-942-5p/HDAC9 pathway.

摘要

动脉粥样硬化(AS)是一种典型的炎症性血管疾病。许多报道证实,环状RNA(circRNA)参与AS的进展。然而,circ_0003204在AS进展中的潜在功能和可能机制仍不明确。使用qRT-PCR和蛋白质免疫印迹法进行表达水平分析。使用细胞计数试剂盒-8(CCK-8)、流式细胞术和蛋白质免疫印迹法检测细胞活力和细胞凋亡。分别通过商业检测试剂盒和ELISA检测氧化应激和炎症状态。通过双荧光素酶报告基因和RNA免疫沉淀试验验证结合关系。氧化型低密度脂蛋白(ox-LDL)增加circ_0003204和组蛋白去乙酰化酶9(HDAC9)水平,并降低miR-942-5p水平。沉默circ_0003204可增强ox-LDL处理的人脐静脉内皮细胞(HUVECs)的细胞活力,并抑制其细胞凋亡、氧化应激和炎症。此外,circ_0003204靶向miR-942-5p以调节ox-LDL导致的HUVECs损伤。而且,miR-942-5p通过靶向HDAC9影响ox-LDL触发的HUVECs损伤。此外,circ_0003204通过诱捕miR-942-5p提高HDAC9表达。circ_0003204通过调节miR-942-5p/HDAC9通路加重ox-LDL诱导的HUVECs损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3efd/8047481/05714b756feb/fcvm-08-646832-g0001.jpg

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