ABSTRACT
[This corrects the article DOI: 10.3389/fphys.2020.00899.].
ABSTRACT
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 CoCl2 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.
ABSTRACT
Circular RNAs (circRNAs), a novel class of endogenous long non-coding RNAs, have attracted considerable attention due to their closed continuous loop structure and potential clinical value. In this study, we investigated the function of circFASTKD1 in vascular endothelial cells. CircFASTKD1 bound directly to miR-106a and relieved its inhibition of Large Tumor Suppressor Kinases 1 and 2, thereby suppressing the Yes-Associated Protein signaling pathway. Under both normal and hypoxic conditions, the ectopic expression of circFASTKD1 reduced the viability, migration, mobility and tube formation of vascular endothelial cells, whereas the downregulation of circFASTKD1 induced angiogenesis by promoting these processes. Moreover, downregulation of circFASTKD1 in mice improved cardiac function and repair after myocardial infarction. These findings indicate that circFASTKD1 is a potent inhibitor of angiogenesis after myocardial infarction and that silencing circFASTKD1 exerts therapeutic effects during hypoxia by stimulating angiogenesis in vitro and in vivo.