Modulation of the Proliferation/Apoptosis Balance of Vascular Smooth Muscle Cells in Atherosclerosis by lncRNA-MEG3 via Regulation of miR-26a/Smad1 Axis
Modulation of the Proliferation/Apoptosis Balance of Vascular Smooth Muscle Cells in Atherosclerosis by lncRNA-MEG3 via Regulation of miR-26a/Smad1 Axis
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DOI：
10.1536/ihj.18-195
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发表时间：
2019-03-01
影响因子：
1.5
通讯作者：
Li, Kunsheng
中科院分区：
文献类型：
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作者：
Bai, Yang;Zhang, Qiangnu;Li, Kunsheng
血管平滑肌细胞（VSMCs）的增殖和凋亡之间的平衡在动脉粥样硬化的发生中起着关键作用。LncRNA-MEG3通过调控内皮细胞的增殖和迁移参与动脉粥样硬化的病理生理过程。其对VSMCs功能障碍的影响及其机制正在积极研究中。本研究发现，在冠状动脉病变组织中，lneRNA-MEG3表达下调与microRNA-26a水平呈负相关。过表达lneRNA-MEG3可抑制VSMCs的增殖，同时促进细胞凋亡。此外，miR-26a/Smad1轴的改变可以拮抗这种作用。生物信息学分析表明，IncRNA-MEG3可以通过互补结合位点与miR-26a相互作用。IncRNA-MEG3的强制表达可降低VSMCs中miR-26a的水平，而Smad1的表达升高。此外，通过双荧光素酶报告基因实验证实了IncRNA-MEG3与miR-26a之间的直接结合，这表明lnc-MEG3可以将miR-26a作为竞争的内源性RNA海绵化。综上所述，我们提出lncRNA-MEG3通过调节miR-26a/Smad1轴调节动脉粥样硬化中VSMCs的增殖/凋亡平衡。
The balance between proliferation and apoptosis of vascular smooth muscle cells (VSMCs) plays a critical role in the initiation of atherosclerosis. LncRNA-MEG3 is involved in the pathophysiology of atherosclerosis through regulation of endothelial cell proliferation and migration. Its effect on the dysfunction of VSMCs and the corresponding mechanisms are actively researched. In this study, we observed that downregulated lneRNA-MEG3 expression was inversely correlated with the microRNA-26a level in coronary artery disease tissues. The overexpression of lneRNA-MEG3 could inhibit VSMCs proliferation while facilitating apoptosis. Moreover, alteration in the miR-26a/Smad1 axis could antagonize this effect. Bioinformatic analysis indicated that IncRNA-MEG3 could interact with miR-26a via complementary binding sites. The enforced expression of IncRNA-MEG3 could reduce the level of miR-26a in VSMCs, while the expression of Smad1 increases. Further, the direct binding between IncRNA-MEG3 and miR-26a was confirmed via dual-luciferase reporter assay, which indicated that lnc-MEG3 could sponge miR-26a as a competing endogenous RNA. In summary, we propose that lncRNA-MEG3 modulates the proliferation/apoptosis balance of VSMCs in atherosclerosis by regulating the miR-26a/Smad1 axis.