---
---
复制标题
DOI：
10.1016/j.jstrokecerebrovasdis.2022.106622
复制
发表时间：
2022-07-06
影响因子：
2.5
通讯作者：
Jiang, Weipeng
中科院分区：
文献类型：
--
作者：
Li, Kunsheng;Cao, Hailong;Jiang, Weipeng
背景本研究旨在探讨lncRNA KCNQ 1 OT 1在氧化低脂蛋白刺激下血管平滑肌细胞中的功能及其调控机制。采用qRT-PCR和蛋白质印迹法检测氧化低脂蛋白处理后VSMCs中KCNQ 1 OT 1、miR-196 a-5 p和FOXO 1的表达水平。采用RNA免疫沉淀、RNA pull-down和双荧光素酶报告基因分析法证实lncRNA KCNQ 1 OT 1、miR-196 a-5 p和FOXO 1之间的相互作用。采用CCK-8和流式细胞术分析KCNQ 1 OT 1、miR-196 a-5 p和FOXO 1的功能。结果体外氧化低脂蛋白处理的VSMCs中KCNQ 1 OT 1和FOXO 1表达降低，同时伴有miR-196 a-5 p的过度表达。KCNQ 1 OT 1作为一种ceRNA，对FOXO 1具有正调节作用，对miR-196 a-5 p具有负调节作用。干扰KCNQ 1 OT 1/miR-196 a-5 p/FOXO 1可以改变氧化低脂蛋白刺激下VSMC的增殖/凋亡失衡。结论KCNQ 1 OT 1/miR-196 a-5 p/FOXO 1通路的异常表达介导了氧化低脂蛋白诱导的VSMCs增殖/凋亡失衡。(c)爱思唯尔公司All rights reserved.
Backgroud The present study aimed to investigate the function and regulatory mechanisms of lncRNA KCNQ1OT1 in vascular smooth muscle cells under oxida-tion low lipoprotein stimulation.Methods RNA sequencing was used to detect transcriptome changes of vascular smooth muscle cells treated with oxidation low lipoprotein. KCNQ1OT1, miR-196a-5p, and FOXO1 expression levels in VSMCs after oxidation low lipoprotein treatment were assessed using qRT-PCR and western blotting. RNA immunopre-cipitation, RNA pull-down, and dual-luciferase reporter assay were used to confirm the interaction among lncRNA KCNQ1OT1, miR-196a-5p, and FOXO1. The func-tions of KCNQ1OT1, miR-196a-5p, and FOXO1 were analyzed by CCK-8 and flow cytometry. The serum samples of high fat-feeding mice and atherosclerosis patients were collected, and the levels of KCNQ1OT1 and miR-196a-5p were analyzed.Results In vitro expression of KCNQ1OT1 and FOXO1 decreased in VSMCs treated with oxidation low lipoprotein, accompanied by overexpression of miR-196a-5p. As a ceRNA, KCNQ1OT1 positively regulated FOXO1 and imparted a negative reg-ulatory effect on miR-196a-5p. Interference KCNQ1OT1/miR-196a-5p/FOXO1 could change roliferation/apoptosis imbalance in VSMCs under oxidation low lipo-protein stimulation. Higher levels of KCNQ1OT1 and lower levels of miR-196a-5p can be found in the thoracic aorta tissues of high fat-feeding mice and serum sam-ples from individuals with carotid atherosclerosis.Conclusion Aberrant expression of KCNQ1OT1/miR-196a-5p/FOXO1 pathway mediated oxidation low lipoprotein-induced proliferation/apoptosis imbalance in VSMCs.(c) 2022 Elsevier Inc. All rights reserved.