FADS1对膀胱癌细胞增殖的影响及其机制研究  

Effects of FADS1 on the proliferation of bladder cancer cells and its mechanism

作　　者：徐涛[1] 柳琦 刘辉勇 占志兵 李有文 王斌[1] XU Tao;LIU Qi;LIU Huiyong;ZHAN Zhibing;LI Youwen;WANG Bin(Department of Urology,Huanggang Central Hospital of Yangtze University,Huanggang 438000,China)

机构地区：[1]长江大学附属黄冈市中心医院,黄冈438000

出　　处：《现代泌尿生殖肿瘤杂志》2024年第6期359-364,共6页Journal of Contemporary Urologic and Reproductive Oncology

基　　金：湖北省自然科学基金青年项目(2022CFB799)。

摘　　要：目的探究脂肪酸去饱和酶1(FADS1)基因对膀胱癌细胞系T24及5637增殖、迁移和自噬激活铁死亡的调控机制。方法在癌症基因组图谱数据库中,对FADS1在膀胱癌中的表达及其对患者预后的影响进行分析,再体外培养膀胱癌细胞系T24及5637,使用Sh RNA敲低FADS1分为NC组和shRNA组,培养75 h,使用平板克隆实验、迁移实验及侵袭实验探究敲低FADS1对细胞增殖和迁移能力的影响,用Western blot检测各组细胞中自噬相关蛋白LC3-Ⅱ、P62、BECN1和铁死亡相关蛋白NCOA4、GXP4的表达。结果FADS1在膀胱癌组织表达量显著高于癌旁组织(P<0.01),它的表达量与肿瘤的淋巴结转移和分期相关(P<0.05),且与FADS1低表达的患者相比,FADS1高表达患者生存率明显降低(P<0.001)。敲低FADS1后,细胞增殖能力降低,自噬相关蛋白LC3-Ⅱ蛋白、BECN1蛋白表达升高,P62蛋白表达降低,铁死亡相关蛋白NCOA4蛋白表达升高,GXP4表达降低。结论敲低FADS1后,膀胱癌细胞细胞增殖减少,并激活了细胞自噬且诱导铁死亡,这说明FADS1可能在膀胱癌的发生、发展中发挥重要作用,为膀胱癌的分子靶向治疗提供了新的理论依据。Objective To investigate the regulatory mechanism of fatty acid desaturase 1(FADS1) for proliferation,migration and autophagy induced ferroptosis in bladder cancer cell lines T24 and 5637.Methods The expression of FADS1 in bladder cancer and its influence on patient prognosis were analyzed in The Cancer Genome Atlas.The bladder cancer cell line T24 and 5637 cells were cultured in vitro,then divided into control group and shRNA group after knockdown of FADS1 with shRNA.The effects of FADS1 knockdown on cell proliferation and migration were investigated by plate cloning,migration and invasion experiments.The expressions of autophagy related proteins LC3-Ⅱ,P62 and BECN1,and ferroptosis related proteins NCOA4 and GXP4 in cells of each group were detected by Western blot.Results The expression of FADS1 in bladder cancer tissues was significantly higher than that in paracancer tissues,and its expression was correlated with lymph node metastasis and stage of tumor.Compared with patients with low expression of FADS1,the survival rate of patients with high expression of FADS1 was significantly lower.After knockdown of FADS1,cell proliferation decreased,autophagy related protein LC3-Ⅱ protein and BECN1 protein expression increased,P62 protein expression decreased,ferroptosis related protein NCOA4 protein expression increased,and GXP4 expression decreased.Conclusions After knockdown of FADS1,cell proliferation of bladder cancer cells decreased,autophagy was activated and ferroptosis was induced.FADS1 may play an important role in the occurrence and development of bladder cancer,which provides a new theoretical basis for molecular targeted therapy of bladder cancer.

关 键 词：脂肪酸去饱和酶1 膀胱癌细胞 细胞自噬 铁死亡 

分 类 号：R737.14[医药卫生—肿瘤]