Circular RNA circ-RELL1 regulates inflammatory response by miR-6873-3p/MyD88/NF-κB axis in endothelial cells
Circular RNA circ-RELL1 regulates inflammatory response by miR-6873-3p/MyD88/NF-κB axis in endothelial cells
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环状RNA circ-RELL1通过miR-6873-3p/MyD88/NF-kB轴调节内皮细胞炎症反应
DOI：
10.1016/j.bbrc.2020.02.109
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发表时间：
2020-04-30
影响因子：
3.1
通讯作者：
Zhu, Peng-li
中科院分区：
文献类型：
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作者：
Huang, Hua-shan;Huang, Xiao-yan;Zhu, Peng-li
内皮炎症是动脉粥样硬化性心血管疾病（ASCVD）的重要病理因素。环状RNA（circRNA）在内皮炎症中的功能和作用仍然未知。在本研究中，我们首先通过高通量circRNA微阵列检测确定circ-RELL 1在ox-LDL诱导的HUVECs中起促炎作用。在ox-LDL诱导的内皮炎症中，敲低circ-RELL 1可降低ICAM 1和VCAM 1的表达。在机制上，circ-RELL 1直接结合细胞质中的miR-6873- 3 p。随后，miR-6873- 3 p降低MyD 88（髓样分化初级应答88）蛋白表达并减轻MyD 88介导的NF-κ B活化。此外，circ-RELL 1可以消除miR-6873- 3 p对炎症反应的抑制作用。我们的研究结果阐明了cycl-RELL 1通过miR-6873- 3 p/MyD 88/NF-κ B轴调控ox-LDL诱导的内皮细胞炎症反应的新途径，为动脉粥样硬化性心血管疾病中内皮炎症的治疗提供了潜在的候选药物。(C)2020作者（S）爱思唯尔公司出版
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-kappa B 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-kappa B axis in ox-LDL induced endothelial cells, which provides a potential therapeutic candidate for endothelium inflammation in atherosclerotic cardiovascular disease. (C) 2020 The Author(s). Published by Elsevier Inc.