山西医科大学学报2025，Vol.56Issue(5)：476-483,8.DOI:10.13753/j.issn.1007-6611.2025.05.003
CISD1对肺癌细胞铁死亡的作用及其机制
Effect and mechanism of CISD1 on ferroptosis in lung cancer cells
摘要
Abstract
Objective To investigate the effect of CDGSH iron-sulfur domain 1(CISD1)on ferroptosis in lung cancer cells and its un-derlying mechanism.Methods The expression of CISD1 in healthy individuals and lung cancer patients,and its effect on prognosis were analyzed using online bioinformatics databases.Human non-small cell lung cancer A549 cells were divided into control group,negative control group(LV-sh-NC),and CISD1 knockdown group(LV-sh-CISD1).Cell cloning experiments were conducted to assess the colony-forming ability of CISD1 knockdown cells in the presence of cellular programmed death inhibitor.BODIPY(581/591)C11 fluorescent probe was used to detect cellular lipid peroxide levels.FerroOrange fluorescent probe was utilized to measure intracellular ferrous ion levels.GSH/GSSG kits were employed to detect glutathione content in A549 cells.Immunofluorescence was conducted to as-sess the levels of ferroptosis-related proteins glutathione peroxidase 4(GPX4)and acyl-CoA synthetase long-chain family member 4(ACSL4).Western blotting was performed to detect the expression levels of iron regulatory protein 2(IRP2)and transferrin receptor(TFR).Results Bioinformatics analysis revealed that CISD1 expression was significantly higher in tissues from patients with lung adenocarcinoma than in healthy individuals(P＜0.05),and the overexpression was associated with poor prognosis(P＜0.05).Compared with negative control group,the cell colony formation ability was significantly reduced in CISD1 knockdown group(P＜0.05).The cell colony formation ability was significantly increased in CISD1 knockdown+ferroptosis inhibitor ferrostatin-1(Fer-1)group compared to CISD1 knockdown group(P＜0.05).Compared with negative control group,the levels of intracellular lipid peroxides and ferrous ions were significantly increased in CISD1 knockdown group(P＜0.05),while the glutathione level was significantly decreased(P＜0.05),the expression of ferroptosis-related protein GPX4 was significantly downregulated(P＜0.05),the expression of ACSL4 was signifi-cantly upregulated(P＜0.05),and the expression levels of iron metabolism-related proteins IRP2 and TFR were both significantly up-regulated(P＜0.05).Conclusion CISD1 is highly expressed in lung cancer cells,and CISD1 knockdown can induce the ferroptosis in lung cancer cells,which may be closely related to the iron metabolism.关键词
肺癌/CISD1/GPX4/ACSL4/铁死亡/铁代谢Key words
lung cancer/CISD1/GPX4/ACSL4/ferroptosis/iron metabolism分类
医药卫生引用本文复制引用
尚文丽,王君,田应选,霍树芬..CISD1对肺癌细胞铁死亡的作用及其机制[J].山西医科大学学报,2025,56(5):476-483,8.基金项目
陕西省重点研发计划项目(2023-YBSF-064) （2023-YBSF-064）
陕西省自然科学基础研究计划重点项目(2022JZ-59) （2022JZ-59）
