Inhibition of hsa-miR-6086 protects human umbilical vein endothelial cells against TNFα-induced proliferation inhibition and apoptosis via CDH5
Inhibition of hsa-miR-6086 protects human umbilical vein endothelial cells against TNFα-induced proliferation inhibition and apoptosis via CDH5
复制标题
抑制 hsa-miR-6086 通过 CDH5 保护人脐静脉内皮细胞免受 TNFα 诱导的增殖抑制和凋亡
DOI：
10.1016/j.gene.2018.03.091
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发表时间：
2018-06-30
期刊：
影响因子：
3.5
通讯作者：
Huang, Zhouqing
中科院分区：
文献类型：
--
作者：
Cai, Xueli;Zhou, Xi;Huang, Zhouqing
miRNAs被认为是一类新的心血管疾病的生物标志物或治疗靶点。Hsa-miR-6086是一种新的mi-RNA，在人胚胎干细胞向内皮细胞分化过程中表达下调。有趣的是，编码钙粘蛋白超家族的经典钙粘蛋白的CDH 5（钙粘蛋白5）是EC的细胞标志物，并且已报道是hsa-miR-6086的靶标。然而，hsa-miR-6086在EC中的作用几乎是未知的。在此，我们报道了hsa-miR-6086在人脐静脉内皮细胞（HUVECs）中被TNF α刺激显著诱导，而CDH 5表达大大降低。重要的是，通过抑制hsa-miR-6086在很大程度上防止了TNF α诱导的CDH 5表达的抑制，并且hsa-miR-6086模拟物大大降低了HUVEC中的CDH 5表达，表明hsa-miR-6086的诱导是TNF α下调CDH 5的原因。此外，通过抑制hsa-miR-6086或外源表达不受hsa-miR-6086影响的CDH 5 cDNA来恢复CDH 5表达水平保护HUVEC免受TNF α诱导的细胞凋亡和细胞生长抑制。综上所述，我们的研究揭示了hsa-miR-6086由TNF α诱导，并通过下调CDH 5表达介导TNF α诱导的HUVEC生长抑制。因此，hsa-miR-6086可能是治疗TNF α诱导的内皮功能障碍的新靶点。
MiRNAs are considered as a novel class of biomarkers or treatment targets for cardiovascular diseases. Hsa-miR-6086, a novel mi-RNA, was reported to be downregulated during the differentiation of human embryonic stem cells into endothelial cells (ECs). Interestingly, CDH5 (cadherin 5), encoding a classical cadherin of the cadherin superfamily, is a cellular marker of ECs and has been reported to be a target of hsa-miR-6086. However, the role of hsa-miR-6086 in ECs is virtually unknown. Herein, we report that hsa-miR-6086 was markedly induced by TNF alpha stimulation in human umbilical vein endothelial cells (HUVECs), whereas CDH5 expression was greatly reduced. Importantly, TNFa-induced suppression of CDH5 expression was largely prevented by inhibiting hsa-miR-6086, and hsa-miR-6086 mimic greatly decrease CDH5 expression in HUVECs, suggesting that the induction of hsa-miR-6086 is responsible for CDH5 downregulation by TNF alpha. In addition, restoration of CDH5 expression level by either inhibiting hsa-miR-6086 or exogenously expressing CDH5 cDNA that is not affected by hsa-miR-6086 protected HUVECs against TNF alpha-induced apoptosis and cell growth inhibition. Taken together, our study reveals that hsa-miR-6086 is induced by TNF alpha and mediates TNF alpha-induced HUVEC growth inhibition through downregulating CDH5 expression. Hence, hsa-miR-6086 might be a new target for treating TNF alpha-induced endothelial dysfunction.