CircIRAK1 aggravates ox-LDL-induced endothelial cell injury in atherosclerosis via TRIM14 upregulation by binding to miR-330-5p.

IF 2.1 4区医学 Q3 HEMATOLOGY Clinical hemorheology and microcirculation Pub Date : 2023-01-01 DOI:10.3233/CH-221551

Fang Liu, Bo Gao, Yu Wang

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引用次数: 5

Abstract

Background: Atherosclerosis (AS) is a common inflammatory cardiovascular disease, and circular RNAs (circRNAs) are associated with the pathogenesis of AS. CircRNA Interleukin (IL)-1 receptor-associated kinase 1 (circIRAK1, hsa_circ_0091822) was upregulated in AS. The aims of this study were to ascertain the function and mechanism of circIRAK1 in AS.

Methods: Human Umbilical Vein Endothelial Cells (HUVECs) were treated with oxidized low-density lipoprotein (ox-LDL). RNA expression was detected by reverse transcription-quantitative polymerase chain reaction assay. Cell viability was examined using Cell Counting Kit-8 assay. Tube formation ability was measured by tube formation assay. Cell apoptosis was assessed using flow cytometry. Western blot was used for protein detection. Inflammatory reaction was evaluated via Enzyme-linked immunosorbent assay. Oxidative injury was analyzed by commercial kits. Target binding was determined through dual-luciferase reporter assay, RNA immunoprecipitation assay and pull-down assay.

Results: The expression of circIRAK1 was upregulated in AS serums and ox-LDL-treated HUVECs. Silencing circIRAK1 enhanced cell viability and angiogenesis while suppressed cell apoptosis, inflammatory response and oxidative stress in ox-LDL-stimulated HUVECs. CircIRAK1 served as a molecular sponge for miR-330-5p. CircIRAK1 regulated ox-LDL-mediated cell injury by absorbing miR-330-5p. In addition, miR-330-5p prevented endothelial cell dysfunction caused by ox-LDL via targeting tripartite motif containing 14 (TRIM14). TRIM14 expression was upregulated by circIRAK1 through sponging miR-330-5p.

Conclusion: These results suggested that circIRAK1 upregulated TRIM14 by interacting with miR-330-5p, consequently contributing to ox-LDL-induced endothelial cell injury in AS.

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CircIRAK1 通过与 miR-330-5p 结合上调 TRIM14，加重动脉粥样硬化中氧化-LDL 诱导的内皮细胞损伤。

背景：动脉粥样硬化（AS）是一种常见的炎症性心血管疾病，循环RNA（circRNA）与AS的发病机制有关。循环RNA白细胞介素（IL）-1受体相关激酶1（circIRAK1，hsa_circ_0091822）在强直性脊柱炎中上调。方法：用氧化低密度脂蛋白（ox-LDL）处理人脐静脉内皮细胞（HUVECs）。用逆转录-定量聚合酶链反应检测 RNA 表达。使用细胞计数试剂盒-8 检测细胞活力。通过试管形成试验检测试管形成能力。使用流式细胞术评估细胞凋亡。采用 Western 印迹法检测蛋白质。通过酶联免疫吸附试验评估炎症反应。氧化损伤通过商业试剂盒进行分析。通过双荧光素酶报告实验、RNA免疫沉淀实验和牵引实验确定目标结合：结果：circIRAK1在AS血清和ox-LDL处理的HUVEC中表达上调。沉默circIRAK1可增强细胞活力和血管生成，同时抑制细胞凋亡、炎症反应和氧化应激。CircIRAK1 是 miR-330-5p 的分子海绵。CircIRAK1 通过吸收 miR-330-5p 来调节 ox-LDL 介导的细胞损伤。此外，miR-330-5p 还能通过靶向含三方基序 14（TRIM14）防止氧化-LDL 导致的内皮细胞功能障碍。TRIM14的表达被circIRAK1通过疏导miR-330-5p而上调：这些结果表明，circIRAK1通过与miR-330-5p相互作用上调了TRIM14，从而导致了氧化-LDL诱导的强直性脊柱炎内皮细胞损伤。

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.