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Identification of microRNA-365 as a negative regulator of endothelial cell proliferation

机译:鉴定microRNA-365作为内皮细胞增殖的负调节剂

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Recent studies have shown that human microRNA miR-365 has significant inhibitory effects on proliferation of transformed cancer cells and vascular smooth muscle cells. However, the effects of miR-365 on proliferation and migration of vascular endothelial cells remain unknown. Using human umbilical vein endothelial cells and in vitro assays, we demonstrated that miR-365 was a suppressor of endothelial cell proliferation, whereas cell migration was not affected by miR-365. We also identified that the expression level of the serine/threonine protein kinase serum- and glucocorticoid-regulated kinase-1 (SGK-1) was regulated by miR-365. The cytostatic effect of miR-365 was mimicked by the specific SGK-1 inhibitor GSK 650394. We further demonstrated that microvesicles isolated from plasma of patients with intracerebral hemorrhage, in which the level of miR-365 was elevated, decreased the expression level of SGK-1, and this effect was abolished in cells pretreated with miR-365 antagomir. However, we did not observe a significant effect of the microvesicles on cell proliferation. It is suggested that miR-365 may have important roles in vascular physiology and/or pathophysiology by modulating endothelial cell proliferation.
机译:最近的研究表明,人类microRNA miR-365对转化的癌细胞和血管平滑肌细胞的增殖具有明显的抑制作用。然而,miR-365对血管内皮细胞增殖和迁移的影响仍然未知。使用人脐静脉内皮细胞和体外测定,我们证明了miR-365是内皮细胞增殖的抑制剂,而细胞迁移不受miR-365的影响。我们还确定了丝氨酸/苏氨酸蛋白激酶血清和糖皮质激素调节激酶1(SGK-1)的表达水平受miR-365调节。特异性SGK-1抑制剂GSK 650394模仿了miR-365的抑制细胞生长的作用。我们进一步证明,从脑出血患者血浆中分离出的微泡(miR-365的水平升高)降低了SGK的表达水平-1,并且在用miR-365 antagomir预处理的细胞中消除了这种作用。但是,我们没有观察到微泡对细胞增殖的显着影响。提示miR-365可能通过调节内皮细胞增殖而在血管生理和/或病理生理中起重要作用。

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