Zeste基因增强子同源物2抑制剂GSK126调控U87细胞株来源胶质瘤干细胞的干性特征  

Enhancer of zeste2 polycomb repressive complex2 inhibitor GSK126 regulates stemness characteristics of U87-derived glioma stem cells

作　　者：赵国政 张卫[1] 冯鸣[2] 周幽心[2] Zhao Guozheng;Zhang Wei;Feng Ming;Zhou Youxin(Department of Neurosurgery,Suzhou Ninth People’s Hospital,Suzhou 215299,China;Department of Neurosurgery,the First Affiliated Hospital of Soochow University,Suzhou 215031,China)

机构地区：[1]苏州大学附属苏州九院神经外科,215299 [2]苏州大学附属第一医院神经外科,215031

出　　处：《中华实验外科杂志》2022年第12期2390-2392,共3页Chinese Journal of Experimental Surgery

摘　　要：目的:观察果蝇zeste基因增强子同源物2(EZH2)抑制剂GSK126对U87来源胶质瘤干细胞(U87s)干性维持、成球及侵袭能力的影响。方法:通过中国胶质瘤基因组图谱(CGGA)数据库,验证EZH2表达对胶质瘤患者预后的影响,同时对比U87与U87s中EZH2的表达水平。免疫磁珠筛选CD133阳性的U87s进行干细胞培养形成稳定传代的胶质瘤干细胞球。通过GSK126和Si-EZH2处理U87s构建GSK126处理组、Si-EZH2处理组、Si-EZH2+GSK126的联合处理组及空白组,来检测U87s干性维持、成球及侵袭能力,组间比较采用独立样本t检验。结果:高表达EZH2患者的生存期明显低于低表达EZH2患者(风险比=1.744,P<0.05)。胶质瘤干细胞中EZH2表达明显高于胶质瘤细胞(0.738±0.024比0.396±0.030,t=8.936,P<0.05)。Si-EZH2处理组的EZH2及下游H3K27me3的表达低于空白组(0.338±0.056比0.926±0.032,t=9.080,P<0.05;0.444±0.034比0.691±0.030,t=5.056,P<0.05)。同时Si-EZH2处理组的干细胞分子标记物CD133、NESTIN表达低于空白组(0.198±0.036比0.824±0.027,t=13.900,P<0.05;0.282±0.023比0.597±0.070,t=4.290,P<0.05)。而GSK126处理组和空白组的EZH2表达无差异,GSK126处理组的H3K27me3、CD133、NESTIN表达低于空白组(0.509±0.044比0.704±0.015,t=4.154,P<0.05;0.249±0.026比0.530±0.025,t=7.763,P<0.05;0.124±0.018比0.424±0.018,t=11.720,P<0.05)。Si-EZH2+GSK126的联合处理组EZH2表达低于GSK126处理组(0.380±0.056比0.735±0.052,t=4.646,P<0.05)。结论:EZH2在胶质瘤干细胞中高表达。GSK126可以通过竞争性抑制EZH2甲基转移酶,从而抑制了U87s的干性特征。Objective To study the effects of enhancer of zeste 2 polycomb repressive complex 2(EZH2)inhibitor GSK126 on stemness maintenance,spheroidization,and invasion ability of U87-derived glioma stem cells(U87s).Methods The Chinese Glioma Genome Atlas(CGGA)database was used to verify the effects of EZH2 expression on the prognosis of glioma patients,and the expression levels of EZH2 in U87 and U87s were compared.Immunomagnetic beads were used to screen CD133-positive U87s for stem cell culture to form stable passaged glioma stem cell spheres.U87s were treated with GSK126 and Si-EZH2 to construct GSK126 treatment group,Si-EZH2 treatment group,Si-EZH2+GSK126 combined treatment group and blank group,so as to detect the stem maintenance,spheroidization and invasion abilities of U87s.The independent sample t test was used for comparison between groups.Results The survival time of patients with high EZH2 expression was significantly lower than that of patients with low expression(Hazard Ratio=1.744,P<0.05).EZH2 expression of glioma stem cells was significantly higher than in glioma cells(0.738±0.024 to 0.396±0.030,t=8.936,P<0.05).The expression of EZH2 and downstream H3K27me3 proteins decreased after Si-EZH2 treatment of U87s(0.338±0.056 to 0.926±0.032,t=9.080,P<0.05),(0.444±0.034 to 0.691±0.030,t=5.056,P<0.05).Additionally,the expression of the stem cell molecular marker CD133 and NESTIN were lower in the blank group(0.198±0.036 to 0.824±0.027,t=13.900.P<0.05;0.282±0.023 to 0.597±0.070,t=4.290,P<0.05).In contrast,there was no difference in the expression of EZH2 between the GSK126 treatment group and the blank group,and the expression of H3K27me3,CD133,and NESTIN were lower in the GSK126 treatment group than in the blank group(0.509±0.044 to 0.704±0.015,t=4.154,P<0.05;0.249±0.026 to 0.530±0.025,t=7.763,P<0.05;0.124±0.018 to 0.424±0.018,t=11.720,P<0.05).However,compared with the GSK126 treatment group,the Si-EZH2+GSK126 combined treatment group showed a significant decrease in EZH2 expression(0.380±0.056 to

关 键 词：胶质瘤干细胞 Zeste基因增强子同源物2 Zeste基因增强子同源物2抑制剂GSK126 

分 类 号：R739.4[医药卫生—肿瘤]