信使核糖核酸
生物
癌细胞
癌症研究
发病机制
心理压抑
基因表达
癌症
癌变
细胞生物学
细胞
基因表达调控
体内
基因
生物化学
免疫学
遗传学
作者
Tong Zhang,Linchong Sun,Yijie Hao,Caixia Suo,Shengqi Shen,Haoran Wei,Wenhao Ma,Pinggen Zhang,Ting Wang,Xuemei Gu,Shiting Li,Zhaolin Chen,Ronghui Yan,Yi Zhang,Yongping Cai,Rongbin Zhou,Weidong Jia,Fang Huang,Ping Gao,Huafeng Zhang
出处
期刊:Nature cancer
[Springer Nature]
日期:2021-12-09
卷期号:3 (1): 75-89
被引量:77
标识
DOI:10.1038/s43018-021-00299-1
摘要
α-Enolase 1 (ENO1) is a critical glycolytic enzyme whose aberrant expression drives the pathogenesis of various cancers. ENO1 has been indicated as having additional roles beyond its conventional metabolic activity, but the underlying mechanisms and biological consequences remain elusive. Here, we show that ENO1 suppresses iron regulatory protein 1 (IRP1) expression to regulate iron homeostasis and survival of hepatocellular carcinoma (HCC) cells. Mechanistically, we demonstrate that ENO1, as an RNA-binding protein, recruits CNOT6 to accelerate the messenger RNA decay of IRP1 in cancer cells, leading to inhibition of mitoferrin-1 (Mfrn1) expression and subsequent repression of mitochondrial iron-induced ferroptosis. Moreover, through in vitro and in vivo experiments and clinical sample analysis, we identified IRP1 and Mfrn1 as tumor suppressors by inducing ferroptosis in HCC cells. Taken together, this study establishes an important role for the ENO1-IRP1-Mfrn1 pathway in the pathogenesis of HCC and reveals a previously unknown connection between this pathway and ferroptosis, suggesting a potential innovative cancer therapy.
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