癌症研究
膀胱癌
癌症
生物
程序性细胞死亡
癌细胞
RNA干扰
细胞凋亡
细胞生物学
核糖核酸
基因
遗传学
作者
Tianyao Liu,Xinyan Xu,Jiazheng Li,Ming Bai,Wenjie Zhu,Yanqing Liu,Siyang Liu,Zihan Zhao,Tianhang Li,Ning Jiang,Yuhao Bai,Qiao Jin,Yulin Zhang,Yufeng Zheng,Shengkai Zhou,Shoubin Zhan,Yu Sun,Gaoli Liang,Yang Luo,Xi Chen,Hongqian Guo,Rong Yang
标识
DOI:10.1038/s41419-023-06333-7
摘要
Abstract Ferroptosis is an iron-dependent form of regulated cell death driven by the lethal lipid peroxides. Previous studies have demonstrated that inducing ferroptosis holds great potential in cancer therapy, especially for patients with traditional therapy failure. However, cancer cells can acquire ferroptosis evasion during progression. To date, the therapeutic potential of inducing ferroptosis in bladder cancer (BCa) remains unclear, and whether a ferroptosis escape mechanism exists in BCa needs further investigation. This study verified that low pathological stage BCa cells were highly sensitive to RSL3-induced ferroptosis, whereas high pathological stage BCa cells exhibited obviously ferroptosis resistance. RNA-seq, RNAi-mediated loss-of-function, and CRISPR/Cas9 experiments demonstrated that ALOX5 deficiency was the crucial factor of BCa resistance to ferroptosis in vitro and in vivo. Mechanistically, we found that ALOX5 deficiency was regulated by EGR1 at the transcriptional level. Clinically, ALOX5 expression was decreased in BCa tissues, and its low expression was associated with poor survival. Collectively, this study uncovers a novel mechanism for BCa ferroptosis escape and proposes that ALOX5 may be a valuable therapeutic target and prognostic biomarker in BCa treatment.
科研通智能强力驱动
Strongly Powered by AbleSci AI