Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, China.
Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, China.
Life Sci. 2020 Sep 15;257:118013. doi: 10.1016/j.lfs.2020.118013. Epub 2020 Jun 27.
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.
新兴文献表明长链非编码 RNA（lncRNA）在动脉粥样硬化进展中具有重要作用。然而，lncRNA 调节动脉粥样硬化的生物学功能和机制仍不清楚。
用氧化型低密度脂蛋白（ox-LDL）处理人脐静脉内皮细胞（HUVECs）。分别用 RT-qPCR 和 Western blot 测定 RNA 和蛋白质水平。用荧光素酶报告基因检测和染色质免疫沉淀（ChIP）检测分子相互作用。用 CCK-8 和划痕愈合实验测定增殖和迁移。
本研究结果显示，lncRNA SNHG7 在 ox-LDL 暴露的 HUVECs 中显著上调。功能获得和缺失实验表明，SNHG7 抑制 HUVECs 的增殖和迁移。机制研究表明，转录因子 E2F1 靶向 lncRNA SNHG7 的启动子区域并加速其表达。此外，miR-186-5p 与 SNHG7 的 3'-UTR 结合，同时 miR-186-5p 也与 MMP2 mRNA 的 3'-UTR 结合。
总之，这些结果表明 E2F1/SNHG7/miR-186-5p/MMP2 轴在血管内皮细胞增殖和迁移中的重要作用，为动脉粥样硬化提供了一个潜在的治疗靶点。
