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 TNFα stimulation in human umbilical vein endothelial cells (HUVECs), whereas CDH5 expression was greatly reduced. Importantly, TNFα-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 TNFα. 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 TNFα-induced apoptosis and cell growth inhibition. Taken together, our study reveals that hsa-miR-6086 is induced by TNFα and mediates TNFα-induced HUVEC growth inhibition through downregulating CDH5 expression. Hence, hsa-miR-6086 might be a new target for treating TNFα-induced endothelial dysfunction.
Keywords: CDH5; Human umbilical vein endothelial cells; Proliferation; TNFα; hsa-miR-6086.
Copyright © 2018 Elsevier B.V. All rights reserved.