circAFF1 Aggravates Vascular Endothelial Cell Dysfunction Mediated by miR-516b/SAV1/YAP1 Axis

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 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.

Circular RNAs in intracranial aneurysms: Emerging roles in pathogenesis, diagnosis and therapeutic intervention

“…However, early events after SAH cause EC dysfunction and cell apoptosis, which in turn exacerbates the delayed phase of SAH pathophysiology [ 34 ]. Wang et al, demonstrated that circAFF1 was upregulated in ECs that under hypoxic conditions by cobalt chloride (CoCl2) and causes ECs to malfunction [ 35 ]. Was demonstrated that upregulation of circAFF1 can suppress the proliferation and tube formation and promote the apoptosis of ECs in vitro.…”

Circular RNA in Acute Central Nervous System Injuries: A New Target for Therapeutic Intervention

“…Recently, the functions of AFF1 in the neural system were investigated. It has been demonstrated that the expression of circAFF1 was upregulated in patients with SAH and overexpression of circAFF1 inhibited the proliferation, tube formation, migration and contributed to apoptosis of endothelial cells ( Wang et al, 2020a ).…”

Circular RNA Expression: Its Potential Regulation and Function in Abdominal Aortic Aneurysms

“…Recent evidence suggests that the hypoxia-induced circAFF1 can lead to disordered vascular ECs through triggering SAV1/YAP1. From the mechanical perspective, the circAFF1/miR-516b/SAV1/YAP1 axis partially contributes to vascular endothelium dysfunction, and it may be used as an indicator of hypoxia injury-induced vascular diseases [ 108 ]. Furthermore, significantly upregulated cZNF609 was observed by Liu et al in HUVECs exposed to hypoxia and HG environments.…”