Xu Xiaonan, Wu Zimu, Qiu Hongyan, Wu Jun
Department of Neurology, Peking University Shenzhen Hospital, Shenzhen 518000, Guangdong Province, People's Republic of China.
Neuropsychiatr Dis Treat. 2021 Jan 22;17:147-156. doi: 10.2147/NDT.S288669. eCollection 2021.
Brain microvascular endothelial cells (BMECs) are involved in brain vascular dysfunction in ischemic stroke. Abnormal expression of circular RNAs regulate physiological and pathophysiological processes in the central nervous system. The aim of the present study was to investigate profile circRNAs in human BMECs after oxygen glucose deprivation (OGD), which was an in vitro model of ischemic stroke, and find promising biomarkers in ischemic stroke.
RNA sequencing (RNA-seq) technology was conducted to analyze the differential expression of circRNAs between BMECs after OGD and non-OGD treated BMECs. RT-qPCR, cell proliferation, cell apoptosis and dual-luciferase assay, and so on, were used to investigate the functions and molecular mechanisms of hsa_circ_0001360 (named circPHC3 in this study) in ischemic stroke.
CircPHC3 was highly expressed in human BMECs after OGD. Knockdown of circPHC3 inhibited cell death and apoptosis in human BMECs treated with OGD. Mechanistically, circPHC3 acted as miR-455-5p sponge to activate TRAF3 to promote cell death and apoptosis in human BMECs after OGD.
In short, circPHC3 promotes cell death and apoptosis in ischemic stroke in vitro model, which might be a novel molecular target for acute cerebrovascular protection.
脑微血管内皮细胞(BMECs)参与缺血性卒中的脑血管功能障碍。环状RNA的异常表达调节中枢神经系统的生理和病理生理过程。本研究旨在研究氧糖剥夺(OGD)后人BMECs中环状RNA的表达谱,OGD是缺血性卒中的体外模型,并寻找缺血性卒中中有前景的生物标志物。
采用RNA测序(RNA-seq)技术分析OGD处理后的BMECs与未处理的BMECs之间环状RNA的差异表达。运用RT-qPCR、细胞增殖、细胞凋亡及双荧光素酶测定等方法研究hsa_circ_0001360(本研究中命名为circPHC3)在缺血性卒中中的功能及分子机制。
circPHC3在OGD后人BMECs中高表达。敲低circPHC3可抑制OGD处理的人BMECs中的细胞死亡和凋亡。机制上,circPHC3作为miR-455-5p的海绵,激活TRAF3以促进OGD后人BMECs中的细胞死亡和凋亡。
简而言之,circPHC3在缺血性卒中体外模型中促进细胞死亡和凋亡,这可能是急性脑血管保护的一个新的分子靶点。