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E2F1/SNHG7/miR-186-5p/MMP2 axis modulates the proliferation and migration of vascular endothelial cell in atherosclerosis
Life Sciences ( IF 5.2 ) Pub Date : 2020-06-27 , DOI: 10.1016/j.lfs.2020.118013
Shengjie Zhang 1 , Xiaotong Zhu 1 , Guangping Li 1
Affiliation  

Emerging literature illustrates critical roles of long noncoding RNAs (lncRNAs) in the progression of atherosclerosis. However, the biological functions and mechanism by which lncRNAs regulate the atherosclerosis remain unclear. Human umbilical vein endothelial cells (HUVECs) were treated with oxidative low-density lipoprotein (ox-LDL). RNA and protein levels were respectively measured using RT-qPCR and western blot. Molecular interaction was detected using luciferase reporter assay and chromatin immunoprecipitation (ChIP). Proliferation and migration were measured using CCK-8 and wound healing assay. Here, results unveiled that lncRNA SNHG7 was remarkedly up-regulated in ox-LDL exposed HUVECs. Gain and loss of function experiments showed that the SNHG7 repressed the proliferation and migration of HUVECs. Mechanistically, transcription factor E2F1 was found to target the promoter region of lncRNA SNHG7 and accelerated its expression. Moreover, miR-186-5p was found to bind with the 3′-UTR of SNHG7, meanwhile miR-186-5p also bound with the MMP2 mRNA 3′-UTR. In conclusion, these results show the essential roles of E2F1/SNHG7/miR-186-5p/MMP2 axis on the proliferation and migration of endothelial cells, providing a potential therapeutic target for atherosclerosis.

中文翻译:

E2F1/SNHG7/miR-186-5p/MMP2轴调节动脉粥样硬化血管内皮细胞的增殖和迁移

新兴文献阐明了长链非编码 RNA (lncRNA) 在动脉粥样硬化进展中的关键作用。然而,lncRNA调节动脉粥样硬化的生物学功能和机制仍不清楚。用氧化低密度脂蛋白(ox-LDL)处理人脐静脉内皮细胞(HUVEC)。分别使用RT-qPCR和蛋白质印迹测量RNA和蛋白质水平。使用荧光素酶报告基因测定和染色质免疫沉淀 (ChIP) 检测分子相互作用。使用CCK-8和伤口愈合测定来测量增殖和迁移。在此,结果表明,lncRNA SNHG7 在 ox-LDL 暴露的 HUVEC 中显着上调。功能获得和丧失实验表明SNHG7抑制HUVEC的增殖和迁移。从机制上讲,转录因子 E2F1 被发现靶向 lncRNA SNHG7 的启动子区域并加速其表达。此外,发现miR-186-5p与SNHG7的3'-UTR结合,同时miR-186-5p也与MMP2 mRNA 3'-UTR结合。总之,这些结果表明E2F1/SNHG7/miR-186-5p/MMP2轴对内皮细胞增殖和迁移的重要作用,为动脉粥样硬化提供了潜在的治疗靶点。
更新日期:2020-06-27
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