EGLN1/c-Myc Induced Lymphoid-Specific Helicase Inhibits Ferroptosis through Lipid Metabolic Gene Expression Changes

doi:10.7150/thno.19988

	EGLN1/c-Myc Induced Lymphoid-Specific Helicase Inhibits Ferroptosis through Lipid Metabolic Gene Expression Changes
	Jiang, Yiqun 3,7,8; Mao, Chao 7,8; Yang, Rui 7,8; Yan, Bin 1,7,8; Shi, Ying 7,8; Liu, Xiaoli 7,8; Lai, Weiwei 7,8; Liu, Yating 7,8; Wang, Xiang 3; Xiao, Desheng 4
刊名	THERANOSTICS
	2017
卷号	7 期号:13 页码:3293-3305
关键词	Ferroptosis LSH WDR76 EGLN1 PHD2 c-Myc HIF-1 alpha SCD1 FADS2 Iron Lipid reactive oxygen species Metabolism Lung cancer
ISSN号	1838-7640
DOI	10.7150/thno.19988
文献子类	Article
英文摘要	Ferroptosis is a newly discovered form of non-apoptotic cell death in multiple human diseases. However, the epigenetic mechanisms underlying ferroptosis remain poorly defined. First, we demonstrated that lymphoid-specific helicase (LSH), which is a DNA methylation modifier, interacted with WDR76 to inhibit ferroptosis by activating lipid metabolism-associated genes, including GLUT1, and ferroptosis related genes SCD1 and FADS2, in turn, involved in the Warburg effect. WDR76 targeted these genes expression in dependent manner of LSH and chromatin modification in DNA methylation and histone modification. These effects were dependent on iron and lipid reactive oxygen species. We further demonstrated that EGLN1 and c-Myc directly activated the expression of LSH by inhibiting HIF-1 alpha. Finally, we demonstrated that LSH functioned as an oncogene in lung cancer in vitro and in vivo. Therefore, our study elucidates the molecular basis of the c-Myc/EGLN1-mediated induction of LSH expression that inhibits ferroptosis, which can be exploited for the development of therapeutic strategies targeting ferroptosis for the treatment of cancer.
资助项目	National Basic Research Program of China[2015CB553903] ; National Natural Science Foundation of China[81372427] ; National Natural Science Foundation of China[81672787] ; National Natural Science Foundation of China[81271763] ; National Natural Science Foundation of China[81672991] ; National Natural Science Foundation of China[81302354] ; National Natural Science Foundation of China[81672307] ; National Natural Science Foundation of China[81422051] ; National Natural Science Foundation of China[81472593]
WOS关键词	CELL LUNG-CANCER ; DNA METHYLATION ; C-MYC ; CHROMATIN ; LSH ; HIF ; TUMOR ; HYPOXIA ; FAMILY ; PROLIFERATION
WOS研究方向	Research & Experimental Medicine
语种	英语
出版者	IVYSPRING INT PUBL
WOS记录号	WOS:000406499400008
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/275705]
专题	分析化学研究室
通讯作者	Tao, Yongguang
作者单位	1.Cent S Univ, Inst Med Sci, Xiangya Hosp, 87 Xiangya Rd, Changsha 410008, Hunan, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, 555 Zu Chongzhi Rd,Zhangjiang Hitech Pk, Shanghai 201203, Peoples R China; 3.Cent S Univ, Dept Thorac Surg, Xiangya Hosp 2, Changsha, Hunan, Peoples R China; 4.Cent S Univ, Dept Pathol, Xiangya Hosp, 87 Xiangya Rd, Changsha 410008, Hunan, Peoples R China; 5.Yale Sch Med, Dept Pathol, New Haven, CT 06520 USA 6.Cent S Univ, Dept Pharmacol, Sch Pharmaceut Sci, Changsha 410078, Hunan, Peoples R China; 7.Cent S Univ, Key Lab Carcinogenesis & Canc Invas, Minist Educ, Xiangya Hosp, 87 Xiangya Rd, Changsha 410008, Hunan, Peoples R China; 8.Cent S Univ, Canc Res Inst, 110 Xiangya Rd, Changsha 410078, Hunan, Peoples R China;
推荐引用方式 GB/T 7714	Jiang, Yiqun,Mao, Chao,Yang, Rui,et al. EGLN1/c-Myc Induced Lymphoid-Specific Helicase Inhibits Ferroptosis through Lipid Metabolic Gene Expression Changes[J]. THERANOSTICS,2017,7(13):3293-3305.
APA	Jiang, Yiqun.,Mao, Chao.,Yang, Rui.,Yan, Bin.,Shi, Ying.,...&Tao, Yongguang.(2017).EGLN1/c-Myc Induced Lymphoid-Specific Helicase Inhibits Ferroptosis through Lipid Metabolic Gene Expression Changes.THERANOSTICS,7(13),3293-3305.
MLA	Jiang, Yiqun,et al."EGLN1/c-Myc Induced Lymphoid-Specific Helicase Inhibits Ferroptosis through Lipid Metabolic Gene Expression Changes".THERANOSTICS 7.13(2017):3293-3305.