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环状 RNA circ-RELL1 通过 miR-6873-3p/MyD88/NF-κB 轴调控内皮细胞炎症反应。

Circular RNA circ-RELL1 regulates inflammatory response by miR-6873-3p/MyD88/NF-κB axis in endothelial cells.

机构信息

Shengli Clinical Medical College of Fujian Medical University, Fuzhou, 350001, Fujian, China; Key Laboratory of Geriatrics, Fujian Provincial Hospital, Fuzhou, 350001, Fujian, China.

Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China.

出版信息

Biochem Biophys Res Commun. 2020 Apr 30;525(2):512-519. doi: 10.1016/j.bbrc.2020.02.109. Epub 2020 Feb 26.

Abstract

Endothelial inflammation is an important contributor to the pathology of atherosclerotic cardiovascular disease (ASCVD). Circular RNAs (circRNAs) function and role in endothelium inflammation still unknown. In our present study, we firstly identified that circ-RELL1 plays a proinflammatory role in ox-LDL-induced HUVECs through high-throughput circRNA microarray assays. Knockdown circ-RELL1 can reduce the expression of ICAM1 and VCAM1 in ox-LDL induced endothelium inflammation. Mechanistically, circ-RELL1 directly bound to miR-6873-3p in cytoplasm. Subsequently miR-6873-3p reduced MyD88 (myeloid differentiation primary response 88) protein expression and alleviated MyD88 medicated NF-κB activation. Furthermore, circ-RELL1 can abolish the inhibition of inflammation response by miR-6873-3p. Our findings illustrate a novel regulatory pathway that circ-RELL1 modulate inflammatory response by miR-6873-3p/MyD88/NF-κB axis in ox-LDL induced endothelial cells, which provides a potential therapeutic candidate for endothelium inflammation in atherosclerotic cardiovascular disease.

摘要

内皮炎症是动脉粥样硬化性心血管疾病(ASCVD)病理学的一个重要贡献者。环状 RNA(circRNA)在血管内皮炎症中的功能和作用尚不清楚。在本研究中,我们通过高通量 circRNA 微阵列分析首次鉴定出 circ-RELL1 在 ox-LDL 诱导的 HUVECs 中发挥促炎作用。circ-RELL1 的敲低可降低 ox-LDL 诱导的内皮炎症中 ICAM1 和 VCAM1 的表达。机制上,circ-RELL1 在细胞质中直接与 miR-6873-3p 结合。随后,miR-6873-3p 降低了 MyD88(髓样分化初级反应 88)蛋白表达并减轻了 MyD88 介导的 NF-κB 激活。此外,circ-RELL1 可以消除 miR-6873-3p 对炎症反应的抑制作用。我们的研究结果阐明了一种新的调节途径,即 circ-RELL1 通过 miR-6873-3p/MyD88/NF-κB 轴调节 ox-LDL 诱导的内皮细胞中的炎症反应,为动脉粥样硬化性心血管疾病中的内皮炎症提供了一个潜在的治疗靶点。

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