circAFF1 Aggravates Vascular Endothelial Cell Dysfunction Mediated by miR-516b/SAV1/YAP1 Axis
circAFF1 Aggravates Vascular Endothelial Cell Dysfunction Mediated by miR-516b/SAV1/YAP1 Axis
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DOI：
10.3389/fphys.2020.00899
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发表时间：
2020-08-05
影响因子：
4
通讯作者：
Tong, Xiao-guang
中科院分区：
文献类型：
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作者：
Wang, Hong-guang;Yan, Hua;Tong, Xiao-guang
缺氧引起的病理性血管内皮损伤是许多血管相关疾病的基础。然而，环状RNA在缺氧血管损伤中的作用仍然知之甚少。我们发现缺氧诱导的AFF 1环状RNA（circAFF 1）可以激活SAV 1/YAP 1，导致血管内皮细胞功能障碍。在HUV-EC-C和HBEC-5i细胞中，circAFF 1在CoCl（2）诱导的缺氧条件下上调。circAFF 1的异常表达可抑制血管内皮细胞的增殖、管腔形成和迁移。circAFF 1的作用是通过吸附miR-516 b释放SAV 1，进而导致YAP 1磷酸化来实现的。此外，我们发现235例蛛网膜下腔出血患者的circAFF 1表达上调。综上所述，我们阐明了circAFF 1/miR-516 b/SAV 1/YAP 1轴在血管内皮功能障碍中的作用及其对血管缺氧损伤所致疾病的潜在早期诊断价值。
Pathological vascular endothelial damage caused by hypoxia is the basis of many vascular-related diseases. However, the role of circular RNA in hypoxic vascular injury is still poorly understood. Here, we found that hypoxia induced AFF1 circular RNA (circAFF1) can activate the SAV1/YAP1 and lead to the dysfunction of vascular endothelial cells. In HUV-EC-C and HBEC-5i cells, circAFF1 was upregulated under CoCl(2)induced hypoxic conditions. The abnormal expression of circAFF1 inhibited the proliferation, tube formation, migration of vascular endothelial cells. The effect of circAFF1 is achieved by the adsorption of miR-516b to release SAV1, which in turn causes the phosphorylation of YAP1. Moreover, we found that the upregulation of circAFF1 in 235 Patients with subarachnoid hemorrhage. Taken together, we clarify the role of circAFF1/miR-516b/SAV1/YAP1 axis in vascular endothelial dysfunction and its potential early diagnostic value of disease caused by hypoxia injury in blood vessels.