Abstract
BackgroundIntracranial 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).MethodsHBVSMCs were exposed to hydrogen peroxide (H2O2). 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.ResultsExposure to H2O2 decreased proliferation and increased apoptosis of HBVSMCs. Circ_DOCK1 expression was reduced in H2O2-treated HBVSMCs. Circ_DOCK1 overexpression rescued H2O2-caused reduction of proliferation and PCNA expression and attenuated H2O2-induced apoptosis and expression of Bcl-2, Bax, and cleaved PARP. MiR-409-3p was targeted by circ_DOCK1 and upregulated in H2O2-treated HBVSMCs. MiR-409-3p upregulation mitigated the role of circ_DOCK1 in proliferation and apoptosis of H2O2-treated HBVSMCs. MCL1 was targeted via miR-409-3p and downregulated via H2O2 treatment. Circ_DOCK1 overexpression enhanced MCL1 expression via modulating miR-409-3p. MiR-409-3p knockdown weakened H2O2-induced proliferation reduction and apoptosis promotion via regulating MCL1.ConclusionCirc_DOCK1 overexpression mitigated H2O2-caused proliferation inhibition and apoptosis promotion in HBVSMCs by modulating miR-409-3p/MCL1 axis.
Highlights
Intracranial aneurysm is an abnormal expansion in the intracranial arteries which could lead to aneurysm rupture (Brinjikji et al, 2016)
myeloid cell leukemia sequence 1 (MCL1) was targeted via miR409-3p and downregulated via H2O2 treatment
Circ_DOCK1, rather than DOCK1, was resistant to RNase R and actinomycin D, indicating circ_DOCK1 had a stable circular structure (Figures 1D,E). These results suggested that the downregulated circ_DOCK1 might be associated with H2O2induced human brain vascular smooth muscle cells (HBVSMCs) injury
Summary
Intracranial aneurysm is an abnormal expansion in the intracranial arteries which could lead to aneurysm rupture (Brinjikji et al, 2016). Smooth muscle cells are responsible in maintaining the vascular structure and are associated with cerebrovascular diseases, including intracranial aneurysm (Frosen and Joutel, 2018). The vascular smooth muscle cell apoptosis can lead to the degradation of vascular wall, inducing the development and rupture of intracranial aneurysm (Liu Z. et al, 2019). Exploring the mechanism of vascular smooth muscle cell proliferation and apoptosis may help in finding novel ways for intracranial aneurysm treatment. Intracranial aneurysm is an abnormal expansion in the intracranial arteries, which is associated with growth and apoptosis of vascular smooth muscle cells. 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)
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