CircRNA DOCK1 Regulates miR-409-3p/MCL1 Axis to Modulate Proliferation and Apoptosis of Human Brain Vascular Smooth Muscle Cells
Xinmin Ding, Xiaolong Wang, Li Han, Zhiyu Zhao, Shuai Jia, Yuanzhao Tuo
Abstract
Background Intracranial aneurysm is an abnormal expansion in the intracranial arteries, which is associated with growth and apoptosis of vascular smooth muscle cells. Circular RNAs (circRNAs) have implicated in the progression of intracranial aneurysms. The purpose of this paper is to study the function and mechanism of circRNA dedicator of cytokinesis 1 (circ_DOCK1) in regulating proliferation and apoptosis of human brain vascular smooth muscle cells (HBVSMCs). Methods HBVSMCs were exposed to hydrogen peroxide (H 2 O 2 ). Cell proliferation and apoptosis were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and flow cytometry, respectively. Circ_DOCK1, microRNA (miR)-409-3p, and myeloid cell leukemia sequence 1 (MCL1) levels were examined by quantitative reverse transcription polymerase chain reaction or western blotting. The target association was assessed by dual-luciferase reporter, RNA pull-down, and RNA immunoprecipitation assays. Results Exposure to H 2 O 2 decreased proliferation and increased apoptosis of HBVSMCs. Circ_DOCK1 expression was reduced in H 2 O 2 -treated HBVSMCs. Circ_DOCK1 overexpression rescued H 2 O 2 -caused reduction of proliferation and PCNA expression and attenuated H 2 O 2 -induced apoptosis and expression of Bcl-2, Bax, and cleaved PARP. MiR-409-3p was targeted by circ_DOCK1 and upregulated in H 2 O 2 -treated HBVSMCs. MiR-409-3p upregulation mitigated the role of circ_DOCK1 in proliferation and apoptosis of H 2 O 2 -treated HBVSMCs. MCL1 was targeted via miR-409-3p and downregulated via H 2 O 2 treatment. Circ_DOCK1 overexpression enhanced MCL1 expression via modulating miR-409-3p. MiR-409-3p knockdown weakened H 2 O 2 -induced proliferation reduction and apoptosis promotion via regulating MCL1. Conclusion Circ_DOCK1 overexpression mitigated H 2 O 2 -caused proliferation inhibition and apoptosis promotion in HBVSMCs by modulating miR-409-3p/MCL1 axis.