Xia Pu, Wen Gui-Min, Zheng Xiao-Hui, Zhao Zhen-Ying
Biological Anthropology Institute, College of Basic Medical Science, Jinzhou Medical University Jinzhou, Liaoning, P. R. China.
Department of Community Nursing, College of Nursing, Jinzhou Medical University Jinzhou, Liaoning, P. R. China.
Am J Cancer Res. 2023 Aug 15;13(8):3659-3667. eCollection 2023.
Ferroptosis results from metabolic dysregulation and is closely linked to liver cancer. Although a ferroptosis-related gene signature in liver cancer has been established, the precise regulatory mechanism is still unclear. To identify shared pathogenic genes linked to ferroptosis across liver cancer patients from diverse racial backgrounds, we evaluated various ferroptosis-related genes, constructing a signature for both Asian and White patients using The Cancer Genome Atlas (TCGA) database. Based on the differential expression and functionality of ferroptosis-associated genes, we selected Farnesyl diphosphate farnesyl transferase 1 (FDFT1), Acyl-CoA synthetase long-chain 4 (ACSL4) and Endoplasmic reticulum membrane protein complex 2 (EMC2) for further study in liver cancer cells. FDFT1, ACSL4 and EMC2 induced ferroptosis of liver cancer cells though upregulation of reactive oxygen species (ROS) levels and downregulation of glutathione peroxidase (GPX4). Current data indicate no notable influence of racial differences on the functionality of ferroptosis-related genes. Our data suggests potential novel therapeutic avenues for liver cancer treatment.
铁死亡由代谢失调引起,与肝癌密切相关。尽管已经建立了肝癌中铁死亡相关基因特征,但精确的调控机制仍不清楚。为了识别不同种族背景的肝癌患者中与铁死亡相关的共同致病基因,我们评估了各种铁死亡相关基因,利用癌症基因组图谱(TCGA)数据库为亚洲和白人患者构建了一个特征。基于铁死亡相关基因的差异表达和功能,我们选择法尼基二磷酸法尼基转移酶1(FDFT1)、酰基辅酶A合成酶长链4(ACSL4)和内质网膜蛋白复合物2(EMC2)在肝癌细胞中进行进一步研究。FDFT1、ACSL4和EMC2通过上调活性氧(ROS)水平和下调谷胱甘肽过氧化物酶(GPX4)诱导肝癌细胞发生铁死亡。目前的数据表明种族差异对铁死亡相关基因的功能没有显著影响。我们的数据为肝癌治疗提示了潜在的新治疗途径。