MAF BZIP转录因子G促进SLC7A11的表达影响头颈磷状细胞癌的铁死亡  

MAF BZIP transcription factor G drives SLC7A11 expression and regulates ferroptosis in head and neck squamous cell carcinoma

作　　者：丁映辉 袁思洁 叶放蕾[1] 王乐[1] Ding Yinghui;Yuan Sijie;Ye Fanglei;Wang Le(Department of Otolaryngology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学第一附属医院耳科,郑州450052

出　　处：《中华实验外科杂志》2025年第1期57-60,共4页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金(82002876)。

摘　　要：目的探讨MAF BZIP转录因子G(MAFG)对头颈磷状细胞癌细胞铁死亡的影响及其作用机制。方法对TCGA数据库的519例头颈磷状细胞癌测序结果进行相关性分析,得到与铁死亡基因SLC7A11相关性>0.5的基因,并从中筛选出SLC7A11的潜在转录因子。将人源头颈磷状细胞癌细胞系SAS和SCC15作为研究对象,分别转染空载质粒和MAFG过表达质粒,转染2 d后,使用平板克隆形成实验验证细胞的增殖能力;使用丙二醛(MDA)检测验证细胞的铁死亡水平;采用蛋白质印迹法(Western blot)实验探索MAFG与SLC7A11之间的关系,并验证其对铁死亡通路的影响。组间比较采用独立样本t检验。结果转录因子MAFG与SLC7A11呈现显著的正相关(P<0.05),且在SLC7A11启动子区域有明显的结合峰。在头颈磷状细胞癌细胞系SAS和SCC15中过表达MAFG后,SLC7A11蛋白水平显著高于对照组(SAS:0.62±0.10比1.02±0.06,t=5.798,P<0.05;SCC15:0.51±0.08比0.95±0.05,t=8.377,P<0.05);MDA水平显著低于对照组(SAS:0.35±0.01比0.98±0.05,t=20.838,P<0.05;SCC15:1.19±0.16比2.22±0.25,t=6.030,P<0.05);克隆形成数显著高于对照组(SAS:443.67±50.65比262.67±25.66,t=5.522,P<0.05;SCC15:520.67±32.13比205.67±19.43,t=14.532,P<0.05)。MAFG过表达同时添加RSL3组相较于MAFG单纯过表达组,MDA水平显著升高(SAS:1.30±0.15比0.39±0.07,t=9.531,P<0.05;SCC15:2.25±0.13比0.96±0.09,t=14.338,P<0.05);克隆形成数显著降低(SAS:304.67±29.67比438.33±25.48,t=5.920,P<0.05;SCC15:170.67±11.37比502.00±39.34,t=14.013,P<0.05)。结论MAFG能够通过MAFG/SLC7A11/铁死亡轴促进头颈磷状细胞癌的进展。Objective To investigate the impact of MAF BZIP transcription factor G(MAFG)on ferroptosis in head and neck squamous cell carcinoma(HNSCC)cells and elucidate its underlying mechanism.Methods Correlation analysis was performed on the sequencing results of 519 HNSCC cases from the TCGA database.Genes with a correlation coefficient greater than 0.5 with the ferroptosis gene SLC7A11 were identified,and potential transcription factors of SLC7A11 were screened from these genes.Human HNSCC cell lines SAS and SCC15 were used as research models.Cells were transfected with either empty vector plasmids or MAFG overexpression plasmids.After 48 h of transfection,the following assays were performed:colony formation assay to assess cell proliferation;malondialdehyde(MDA)assay to evaluate ferroptosis levels;Western blotting analysis to explore the relationship between MAFG and SLC7A11 and to validate its effect on the ferroptosis pathway.Statistical comparisons between experimental groups were performed using independent sample t-tests.Results The transcription factor MAFG showed a significant positive correlation with SLC7A11(P<0.05),with a notable binding peak in the promoter region of SLC7A11.Overexpression of MAFG in SAS and SCC15 cell lines significantly increased SLC7A11 protein levels compared to the control group(SAS:0.62±0.10 vs.1.02±0.06,t=5.798,P<0.05;SCC15:0.51±0.08 vs.0.95±0.05,t=8.377,P<0.05).The MAFG-overexpression group showed significantly reduced MDA levels compared to the control group(SAS:0.35±0.01 vs.0.98±0.05,t=20.838,P<0.05;SCC15:1.19±0.16 vs.2.22±0.25,t=6.030,P<0.05).Similarly,the number of colonies formed was significantly greater in the MAFG-overexpression group than the control group(SAS:443.67±50.65 vs.262.67±25.66,t=5.522,P<0.05;SCC15:520.67±32.13 vs.205.67±19.43,t=14.532,P<0.05).In the MAFG-overexpression group treated with RSL3(a ferroptosis inducer),MDA levels were significantly increased compared to the MAFG-overexpression group(SAS:1.30±0.15 vs.0.39±0.07,t=9.531,P<0.05;SCC15:2.25±

关 键 词：头颈磷状细胞癌 铁死亡 MAF BZIP转录因子G 

分 类 号：R739.91[医药卫生—肿瘤]