Wu Shanwu, Yang Sheng, Qu Hongyan
Department of Neurosurgery, Sinopharm Dongfeng General Hospital, No. 16 Daling Road, Zhangwan District, Shiyan City, 442000, Hubei, China.
Open Life Sci. 2021 Sep 29;16(1):1053-1063. doi: 10.1515/biol-2021-0082. eCollection 2021.
Oxidized low-density lipoprotein (ox-LDL) is a significant risk factor for various brain vascular diseases. Circular RNA (circRNA) is involved in the pathogenesis of brain vascular diseases. This study revealed the roles of circ_CHFR in ox-LDL-mediated cell proliferation, apoptosis, and endothelial-to-mesenchymal transition (EndoMT). Our results showed that circ_CHFR and EGFR expressions were dramatically upregulated, while miR-15a-5p expression was downregulated in ox-LDL-induced human brain microvessel endothelial cells (HBMECs) relative to control groups. circ_CHFR knockdown hindered the effects of ox-LDL exposure on cell proliferation, cell cycle, apoptosis, and EndoMT in HBMECs, whereas these impacts were abolished by miR-15a-5p inhibitor. In addition, circ_CHFR functioned as a sponge of miR-15a-5p and miR-15a-5p bound to EGFR. Thus, we concluded that circ_CHFR silencing hindered ox-LDL-mediated cell proliferation, apoptosis, and EndoMT by downregulating EGFR expression through sponging miR-15a-5p in HBMECs. Our findings provide a new mechanism for studying circRNA-directed therapy in ox-LDL-induced human brain vascular diseases.
氧化型低密度脂蛋白(ox-LDL)是多种脑血管疾病的重要危险因素。环状RNA(circRNA)参与脑血管疾病的发病机制。本研究揭示了circ_CHFR在ox-LDL介导的细胞增殖、凋亡和内皮-间充质转化(EndoMT)中的作用。我们的结果表明,相对于对照组,在ox-LDL诱导的人脑微血管内皮细胞(HBMECs)中,circ_CHFR和表皮生长因子受体(EGFR)的表达显著上调,而miR-15a-5p的表达下调。circ_CHFR基因敲低阻碍了ox-LDL暴露对HBMECs细胞增殖、细胞周期、凋亡和EndoMT的影响,而这些影响被miR-15a-5p抑制剂消除。此外,circ_CHFR充当miR-15a-5p的海绵,且miR-15a-5p与EGFR结合。因此,我们得出结论,circ_CHFR沉默通过在HBMECs中充当miR-15a-5p的海绵来下调EGFR表达,从而阻碍ox-LDL介导的细胞增殖、凋亡和EndoMT。我们的研究结果为研究circRNA导向治疗ox-LDL诱导的人脑血管疾病提供了一种新机制。