miR-214 protects erythroid cells against oxidative stress by targeting ATF4 and EZH2

CORC > 生态环境研究中心 > 中国科学院生态环境研究中心 > 环境化学与生态毒理学国家重点实验室

	miR-214 protects erythroid cells against oxidative stress by targeting ATF4 and EZH2
	Gao, Ming; Liu, Yun; Chen, Yue; Yin, Chunyang; Chen, Jane-Jane; Liu, Sijin
刊名	FREE RADICAL BIOLOGY AND MEDICINE
	2016-03
卷号	92 期号:0 页码:39-49
关键词	miR-214 Nrf2 ATF4 EZH2 Erythroid cells
英文摘要	Nuclear factor (erythroid-derived 2) like 2 (Nrf2) is a key regulator in protecting cells against stress by targeting many anti-stress response genes. Recent evidence also reveals that Nrf2 functions partially by targeting mircroRNAs (miRNAs). However, the understanding of Nrf2-mediated cytoprotection through miRNA-dependent mechanisms is largely unknown. In the current study, we identified a direct Nrf2 targeting miRNA, miR-214, and demonstrated a protective role of miR-214 in erythroid cells against oxidative stresses generated by radiation, excess iron and arsenic (As) exposure. miR-214 expression was transcriptionally repressed by Nrf2 through a canonical antioxidant response element (ARE) within its promoter region, and this repression is ROS-dependence. The suppression of miR-214 by Nrf2 could antagonize oxidative stress-induced cell death in erythroid cells by two ways. First, miR-214 directly targeted ATF4, a crucial transcriptional factor involved in anti-stress responses, down regulation of miR-214 releases the repression of ATF4 translation and leads to increased ATF4 protein content. Second, miR-214 was able to prevent cell death by targeting EZH2, the catalytic core component of PRC2 complex that is responsible for tri-methylation reaction at lysine 27 (K27) of histone 3 (H3) (H3K27me3), by which As induced miR-214 reduction resulted in an increased global H3K27me3 level and a compromised over expression of a pro-apoptotic gene Bim. These two pathways downstream of miR-214 synergistically cooperated to antagonize erythroid cell death upon oxidative stress. Our combined data revealed a protective role of miR-214 signaling in erythroid cells against oxidative stress, and also shed new light on Nrf2-mediated cytoprotective machinery. (C) 2016 Elsevier Inc. All rights reserved.
收录类别	SCI
内容类型	期刊论文
源URL	[http://ir.rcees.ac.cn/handle/311016/35896]
专题	生态环境研究中心_环境化学与生态毒理学国家重点实验室
推荐引用方式 GB/T 7714	Gao, Ming,Liu, Yun,Chen, Yue,et al. miR-214 protects erythroid cells against oxidative stress by targeting ATF4 and EZH2[J]. FREE RADICAL BIOLOGY AND MEDICINE,2016,92(0):39-49.
APA	Gao, Ming,Liu, Yun,Chen, Yue,Yin, Chunyang,Chen, Jane-Jane,&Liu, Sijin.(2016).miR-214 protects erythroid cells against oxidative stress by targeting ATF4 and EZH2.FREE RADICAL BIOLOGY AND MEDICINE,92(0),39-49.
MLA	Gao, Ming,et al."miR-214 protects erythroid cells against oxidative stress by targeting ATF4 and EZH2".FREE RADICAL BIOLOGY AND MEDICINE 92.0(2016):39-49.