zeste同源物2的增强子和人类mutL同源物1通过激活丝裂原细胞外激酶/细胞外信号调节激酶途径调控神经胶质瘤的增殖  

Inhibition of enhancer of zeste homolog 2 and human mutL homolog 1 suppresses progression of glioma

作　　者：张红赟[1] 邢振义[1] 张风江[2] 董剑锋 郑杰[1] Zhang Hongyun;Xing Zhenyi;Zhang Fengjiang;Dong Jianfeng;Zheng Jie(Department of Neurosurgery,Xinxiang Central Hospital,Xinxiang 453000,China;Department of Neurosurgery,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]新乡市中心医院神经外科,新乡453000 [2]郑州大学第一附属医院神经外科,郑州450052

出　　处：《中华实验外科杂志》2024年第5期983-986,共4页Chinese Journal of Experimental Surgery

摘　　要：目的:探讨zeste同源物2的增强子(EZH2)和人类mutL同源物1(hMLH1)在神经胶质瘤中的作用。方法:设计合成靶向抑制EZH2和hMLH1和hMLH1特异的小干扰RNA(siRNA),转染U-87细胞,分为对照组和敲低组,通过5-乙炔基-2’脱氧尿嘧啶核苷(EdU)增殖实验分析两组的增殖能力。采用t检验进行组间比较。结果:神经胶质瘤组织和细胞中EZH2(7.97±0.14、6.00±0.18、6.24±0.11,t=83.80、47.18、83.55)和hMLH1(6.15±0.08、3.93±0.17、4.25±0.12,t=103.700、29.800、45.510)的mRNA水平明显高于对照组(P<0.01)。U-87胶质瘤细胞的siRNA转染导致细胞增殖能力降低,对照组(68.2±14.8),EZH2敲低组(33.5±13.1),hMLH1敲低组(43.1±10.0)。敲低EZH2和hMLH1表达后增强转染细胞凋亡(t=3.041、2.934,P<0.05)。沉默后磷酸化丝裂原细胞外激酶1(p-MEK1)/丝裂原细胞外激酶1(MEK1)和磷酸化细胞外信号调节激酶(p-ERK1)/细胞外信号调节激酶(ERK1)的比例下调,p-MEK(t=5.590、6.548,P<0.05)和p-ERK1的水平降低(t=10.730、9.260,P<0.05)。与单独转染EZH2-siRNA和hMLH1-siRNA比较,EZH2-siRNA和hMLH1-siRNA共转染的U-87细胞中,抑制作用增强(t=6.425、7.273,P<0.05)。结论:对EZH2和hMLH1的抑制可能通过激活MEK/ERK途径影响神经胶质瘤的生长和细胞死亡。Objective To investigate the role of enhancer of zeste homolog 2(EZH2)and human mutL homolog 1(hMLH1)in glioma.Methods The small interfering RNA(siRNA)targeting EZH2 and hMLH1 was designed and synthesized,and transfected into U-87 cells.The control group and knockdown group were set up,and the proliferation of the two groups was analyzed through 5-Ethynyl-2′-deoxyuridine(EdU)proliferation assay.T test was used for comparison between groups.Results The results showed that the mRNA levels of EZH2(7.97±0.14,6.00±0.18,6.24±0.11,t=83.80,47.18,83.55)and hMLH1(6.15±0.08,3.93±0.17,4.25±0.12,t=103.700,29.800,45.510)were significantly higher in glioma tissues and cells than their normal counterparts(P<0.01).Transfection of siRNA into U-87 glioma cells resulted in decreased cell proliferation capacity,with the control group being(68.2±14.8),EZH2 knockdown group being(33.5±13.1),and hMLH1 knockdown group being(43.1±10.0).After knocking down EZH2 and hMLH1 expression,cell apoptosis of transfected cells was enhanced(t=3.041,2.934,P<0.05).The ratio of p-MEK1/MEK1 and p-ERK1/ERK1 was down-regulated after silencing the level of p-MEK(t=5.590,6.548,P<0.05)and p-ERK1(t=10.730,9.260,P<0.05).The inhibitory effects were enhanced(t=6.425,7.273,P<0.05)in U-87 cells that were co-transfected with EZH2-siRNA and hMLH1-siRNA as compared with those that were transfected individually.Conclusion The findings show that the inhibition of EZH2 and hMLH1 impacts glioma growth and cell death likely via in-activating the MEK/ERK pathway.

关 键 词：神经胶质瘤 增殖 丝裂原细胞外激酶 

分 类 号：R739.4[医药卫生—肿瘤]