General Hospital of Chinese People's Liberation Army, Beijing 100853, PR China.
Beijing Institute of Basic Medical Sciences, Beijing 100850, PR China.
FEBS Lett. 2014 Jun 5;588(12):2063-9. doi: 10.1016/j.febslet.2014.04.037. Epub 2014 May 8.
As a cleavage enzyme of precursor TNF-α, the high expression level of ADAM17 in endothelial cells is an important factor in atherosclerosis. In this study, we demonstrate that ADAM17 is the target of miR-152. We found that miR-152 could reduce TNF precursor cleavage and inhibit cell proliferation and migration by targeting ADAM17 in human umbilical vein endothelial cells (HUVECs). Furthermore, the expression pattern of miR-152 and corresponding target ADAM17 was opposite in HUVECs under hypoxic conditions. The levels of circulating miR-152 in AS patient sera were lower than those detected in the sera of normal individuals. Our results indicate that miR-152 may be involved in the development of human atherosclerosis and could be used as diagnostic biomarker or therapeutic target in atherosclerosis.
作为前体 TNF-α 的切酶，ADAM17 在血管内皮细胞中的高表达水平是动脉粥样硬化的一个重要因素。在本研究中，我们证明 ADAM17 是 miR-152 的靶标。我们发现 miR-152 可以通过靶向人脐静脉内皮细胞（HUVEC）中的 ADAM17 来减少 TNF 前体的切割，并抑制细胞增殖和迁移。此外，在缺氧条件下，HUVEC 中 miR-152 和相应靶标 ADAM17 的表达模式相反。AS 患者血清中的循环 miR-152 水平低于正常人血清中的检测水平。我们的结果表明，miR-152 可能参与了人类动脉粥样硬化的发生，可作为动脉粥样硬化的诊断生物标志物或治疗靶点。
