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环状CHFR通过miR-15a-5p/表皮生长因子受体轴调控人脑海微血管内皮细胞中氧化型低密度脂蛋白介导的细胞增殖、凋亡和内皮-间充质转化。

circ_CHFR regulates ox-LDL-mediated cell proliferation, apoptosis, and EndoMT by miR-15a-5p/EGFR axis in human brain microvessel endothelial cells.

作者信息

Wu Shanwu, Yang Sheng, Qu Hongyan

机构信息

Department of Neurosurgery, Sinopharm Dongfeng General Hospital, No. 16 Daling Road, Zhangwan District, Shiyan City, 442000, Hubei, China.

出版信息

Open Life Sci. 2021 Sep 29;16(1):1053-1063. doi: 10.1515/biol-2021-0082. eCollection 2021.

DOI:10.1515/biol-2021-0082
PMID:34676300
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8483062/
Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c3c/8483062/5ed450bb8571/j_biol-2021-0082-fig007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c3c/8483062/18dbdd477656/j_biol-2021-0082-fig001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c3c/8483062/38abb0e3b99b/j_biol-2021-0082-fig002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c3c/8483062/76d3ec6dface/j_biol-2021-0082-fig003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c3c/8483062/f9cd6e518bea/j_biol-2021-0082-fig004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c3c/8483062/fc848c833027/j_biol-2021-0082-fig005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c3c/8483062/a509880c737b/j_biol-2021-0082-fig006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c3c/8483062/5ed450bb8571/j_biol-2021-0082-fig007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c3c/8483062/18dbdd477656/j_biol-2021-0082-fig001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c3c/8483062/38abb0e3b99b/j_biol-2021-0082-fig002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c3c/8483062/76d3ec6dface/j_biol-2021-0082-fig003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c3c/8483062/f9cd6e518bea/j_biol-2021-0082-fig004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c3c/8483062/fc848c833027/j_biol-2021-0082-fig005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c3c/8483062/a509880c737b/j_biol-2021-0082-fig006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c3c/8483062/5ed450bb8571/j_biol-2021-0082-fig007.jpg

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