Circ_0091822 aggravates ox-LDL-induced endothelial cell injury through targeting the miR-661/RAB22A axis.

IF 2.1 4区医学 Q3 HEMATOLOGY Clinical hemorheology and microcirculation Pub Date : 2023-01-01 DOI:10.3233/CH-221453

Lingfeng Zhu, Ping Zhao, Xianwei Meng, Hong Jin, Baojuan Tuo

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引用次数: 10

Abstract

Background: Endothelial dysfunction is considered to be an important factor in the pathogenesis of atherosclerosis. Circular RNAs (circRNAs) have been confirmed to participate in the development of atherosclerosis. Nevertheless, the role and mechanism of circ_0091822 in atherosclerosis have not been studied yet.

Methods: The expression of circ_0091822, miR-661 and RAB22A were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). The levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were estimated by enzyme-linked immunosorbent assay (ELISA). Cell viability was analyzed by Cell Counting Kit-8 (CCK-8) assay, cell proliferation was evaluated by EdU assay, and cell apoptosis was gauged by flow cytometry. Western blot was performed to assess the protein levels of Bax, Cleaved-caspase-3 and RAB22A. The interaction among miR-661 and circ_0091822 or RAB22A was verified by dual-luciferase reporter assayRESULTS:Ox-LDL enhanced the expression of circ_0091822 in HUVECs. It also constrained proliferation, promotes apoptosis and inflammation in HUVECs, and down-regulation of circ_0091822 attenuated these effects. Mechanically, circ_0091822 could serve as a sponge of miR-661, miR-661 interference rescued circ_0091822 inhibition-mediated effect on the biological functions in ox-LDL-induced HUVECs. Additionally, RAB22A was a target of miR-661, and its overexpression could partially overturn the negative regulation of miR-661 on ox-LDL-treated HUVECs injury. Importantly, circ_0091822 sponged miR-661 to positively regulate RAB22A expression.

Conclusion: Circ_0091822 contributed to cell injury by targeting miR-661/RAB22A axis in ox-LDL-stimulated HUVECs.

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Circ_0091822通过靶向miR-661/RAB22A轴加重ox- ldl诱导的内皮细胞损伤。

背景:内皮功能障碍被认为是动脉粥样硬化发病的重要因素。环状rna (circRNAs)已被证实参与动脉粥样硬化的发展。然而，circ_0091822在动脉粥样硬化中的作用和机制尚未被研究。方法:采用实时荧光定量聚合酶链式反应(qRT-PCR)分析circ_0091822、miR-661和RAB22A的表达。采用酶联免疫吸附试验(ELISA)测定各组小鼠白细胞介素-6 (IL-6)和肿瘤坏死因子-α (TNF-α)水平。细胞计数试剂盒-8 (CCK-8)法检测细胞活力，EdU法检测细胞增殖，流式细胞术检测细胞凋亡。Western blot检测Bax、Cleaved-caspase-3、RAB22A蛋白表达水平。通过双荧光素酶报告基因检测证实了miR-661与circ_0091822或RAB22A之间的相互作用。结果:Ox-LDL增强了huvec中circ_0091822的表达。它还能抑制HUVECs的增殖、促进细胞凋亡和炎症，而下调circ_0091822可减弱这些作用。机械上，circ_0091822可以作为miR-661的海绵，miR-661的干扰挽救了circ_0091822对ox- ldl诱导的HUVECs生物学功能的抑制介导作用。此外，RAB22A是miR-661的靶点，其过表达可以部分推翻miR-661对ox- ldl处理的HUVECs损伤的负调控。重要的是，circ_0091822海绵miR-661正向调节RAB22A的表达。结论:Circ_0091822在ox- ldl刺激的huvec中通过靶向miR-661/RAB22A轴参与细胞损伤。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical hemorheology and microcirculation 医学-外周血管病

CiteScore

4.30

自引率

33.30%

发文量

170

期刊介绍： Clinical Hemorheology and Microcirculation, a peer-reviewed international scientific journal, serves as an aid to understanding the flow properties of blood and the relationship to normal and abnormal physiology. The rapidly expanding science of hemorheology concerns blood, its components and the blood vessels with which blood interacts. It includes perihemorheology, i.e., the rheology of fluid and structures in the perivascular and interstitial spaces as well as the lymphatic system. The clinical aspects include pathogenesis, symptomatology and diagnostic methods, and the fields of prophylaxis and therapy in all branches of medicine and surgery, pharmacology and drug research. The endeavour of the Editors-in-Chief and publishers of Clinical Hemorheology and Microcirculation is to bring together contributions from those working in various fields related to blood flow all over the world. The editors of Clinical Hemorheology and Microcirculation are from those countries in Europe, Asia, Australia and America where appreciable work in clinical hemorheology and microcirculation is being carried out. Each editor takes responsibility to decide on the acceptance of a manuscript. He is required to have the manuscript appraised by two referees and may be one of them himself. The executive editorial office, to which the manuscripts have been submitted, is responsible for rapid handling of the reviewing process. Clinical Hemorheology and Microcirculation accepts original papers, brief communications, mini-reports and letters to the Editors-in-Chief. Review articles, providing general views and new insights into related subjects, are regularly invited by the Editors-in-Chief. Proceedings of international and national conferences on clinical hemorheology (in original form or as abstracts) complete the range of editorial features.