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MicroRNA-520c-3p targeting of RelA/p65 suppresses atherosclerotic plaque formation
The International Journal of Biochemistry & Cell Biology ( IF 3.4 ) Pub Date : 2020-11-06 , DOI: 10.1016/j.biocel.2020.105873
Jingyu Wang 1 , Xiaoyan Hu 1 , Xinxin Hu 1 , Fuhua Gao 1 , Mei Li 1 , Ying Cui 2 , Xiaoqing Wei 2 , Yuanhua Qin 3 , Chenghong Zhang 4 , Ying Zhao 2 , Ying Gao 5
Affiliation  

Atherosclerosis is a chronic inflammatory disease, and it’s the leading cause of death worldwide. Dysregulation of microRNAs (miRNAs) has been found to be associated with atherosclerosis. miR-520c-3p has been implicated in several types of cancer. However, little is known about the role of miR-520c-3p in atherosclerosis. In this study, we found that miR-520c-3p agomir decreased atherosclerotic plaque size, collagen content, the quantity of PCNA-positive cell and RelA/p65 expression of vascular smooth muscle cells (VSMCs) in the aortic valve of apoE−/− mice in vivo. The possible mechanisms of the protective effects of miR-520c-3p on atherosclerotic mice were then investigated in VSMCs. in vitro experiments showed that miR-520c-3p expressions were significantly reduced in human aortic vascular smooth muscle cell (HASMCs) treated with platelet-derived growth factor (PDGF-BB). miR-520c-3p mimics repress PDGF-BB-mediated the proliferation, migration and decrease in the percentage of cells in G2/M phase, which was associated with downregulation of RelA/p65. Mechanistically, miRNA pull-down, luciferase reporter and mRNA stability assays confirmed miR-520c-3p mimics was able to directly target 3′-UTR of RelA/p65 mRNA and decreased half-life of RelA/p65 mRNA in HASMCs. Overexpression of RelA/p65 reversed the inhibition of cell proliferation induced by miR-520c-3p mimics in HASMCs. In conclusion, our findings suggest that miR-520c-3p inhibits PDGF-BB-mediated the proliferation and migration of HASMCs by targeting RelA/p65, which may provide potential therapeutic strategies in atherosclerosis treatment.



中文翻译:

靶向 RelA/p65 的 MicroRNA-520c-3p 抑制动脉粥样硬化斑块形成

动脉粥样硬化是一种慢性炎症性疾病,是世界范围内导致死亡的主要原因。已发现微小 RNA (miRNA) 的失调与动脉粥样硬化有关。miR-520c-3p 与多种癌症有关。然而,关于 miR-520c-3p 在动脉粥样硬化中的作用知之甚少。在这项研究中,我们发现 miR-520c-3p agomir 降低了apoE主动脉瓣中动脉粥样硬化斑块的大小、胶原蛋白含量、PCNA 阳性细胞的数量和血管平滑肌细胞 (VSMCs) 的 RelA/p65 表达-/-小鼠体内。然后在 VSMC 中研究了 miR-520c-3p 对动脉粥样硬化小鼠的保护作用的可能机制。体外实验表明,用血小板衍生生长因子(PDGF-BB)处理的人主动脉血管平滑肌细胞(HASMCs)中,miR-520c-3p的表达显着降低。miR-520c-3p 模拟物抑制 PDGF-BB 介导的增殖、迁移和 G2/M 期细胞百分比的降低,这与 RelA/p65 的下调有关。从机制上讲,miRNA 下拉、荧光素酶报告基因和 mRNA 稳定性测定证实 miR-520c-3p 模拟物能够直接靶向 RelA/p65 mRNA 的 3'-UTR 并缩短 HASMC 中 RelA/p65 mRNA 的半衰期。RelA/p65 的过表达逆转了 HASMC 中由 miR-520c-3p 模拟物诱导的细胞增殖抑制。综上所述,

更新日期:2021-01-06
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