EGLN1/c-Myc Induced Lymphoid-Specific Helicase Inhibits Ferroptosis through Lipid Metabolic Gene Expression Changes.
EGLN1/c-Myc Induced Lymphoid-Specific Helicase Inhibits Ferroptosis through Lipid Metabolic Gene Expression Changes.
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EGLN1/c-Myc 诱导的淋巴特异性解旋酶通过脂质代谢基因表达变化抑制铁死亡
作者：
Jiang Y;Mao C;Yang R;Yan B;Shi Y;Liu X;Lai W;Liu Y;Wang X;Xiao D;Zhou H;Cheng Y;Yu F;Cao Y;Liu S;Yan Q;Tao Y
铁下垂是人类多种疾病中一种新发现的非凋亡细胞死亡形式。然而，铁下垂的表观遗传机制仍然不明确。首先，我们证明了淋巴细胞特异性解旋酶（LSH）是一种DNA甲基化修饰因子，它通过激活脂质代谢相关基因（包括GLUT1）和铁亡相关基因SCD1和FADS2)与WDR76相互作用来抑制铁亡，进而参与Warburg效应。WDR76以依赖LSH和染色质修饰的方式靶向这些基因在DNA甲基化和组蛋白修饰中的表达。这些作用依赖于铁和脂质活性氧。我们进一步证明EGLN1和c-Myc通过抑制HIF-1α直接激活LSH的表达。最后，我们证明了LSH在体外和体内作为肺癌的致癌基因起作用。因此，我们的研究阐明了c-Myc/ egln1介导的LSH表达抑制铁下垂的分子基础，可用于开发针对铁下垂治疗癌症的治疗策略。
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-1α. 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.
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染色质重塑因子 LSH 通过抑制富马酸水合酶的活性来驱动癌症进展
影响因子：
11.2
作者：
He X;Yan B;Liu S;Jia J;Lai W;Xin X;Tang CE;Luo D;Tan T;Jiang Y;Shi Y;Liu Y;Xiao D;Chen L;Liu S;Mao C;Yin G;Cheng Y;Fan J;Cao Y;Muegge K;Tao Y
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Tao Y
影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
影响因子：
4
作者：
Burrage, Joe;Termanis, Ausma;Stancheva, Irina
通讯作者：
Stancheva, Irina
染色质修饰与暂停 RNA 聚合酶 II 在停滞基因和激活基因之间动态转换中的相互作用
影响因子：
10
作者：
Liu, Shuang;Tao, Yongguang
通讯作者：
Tao, Yongguang
影响因子：
12.4
作者：
Lin YJ;Shyu WC;Chang CW;Wang CC;Wu CP;Lee HT;Chen LJ;Hsieh CH
通讯作者：
Hsieh CH