EZH2在恶性胸膜间皮瘤中的作用机制研究  

A Mechanism of EZH2 in Malignant Pleural Mesothelioma

作　　者：高胜男[1] 张明昱 都兰 乌日罕[1] 曹冉华[1] 贾永峰[1] 张嘉玲[1] 呼群[1] GAO Sheng-nan;ZHANG Ming-yu;DU Lan;WURi-lian;CAO Ran-hua;JIA YOng-leng;ZHANG Jia-ling;HU Qun(Inner Mongolia Me diced University Affiliated Hospital,Hohhot 010030,China;Department of Basic Medicine.Inner Mongolia Medical University,Hohhot 010030,China)

机构地区：[1]内蒙古医科大学附属医院,内蒙古呼和浩特010030 [2]内蒙古医科大学基础医学院,内蒙古呼和浩特010030

出　　处：《肿瘤学杂志》2019年第12期1070-1074,共5页Journal of Chinese Oncology

基　　金：国家自然科学基金（81160253）;内蒙古自治区肿瘤生物协同创新培育中心项目（1619002010）;内蒙古自然科学基金（2017MS0830)

摘　　要：[目的]探讨恶性胸膜间皮瘤中EZH2、Cul4A、Gli1的表达及其相互作用关系。[方法] Real-time PCR检测恶性间皮瘤细胞株H2452、MSTO-211H以及人正常间皮细胞株Met-5A中EZH2、Cul4A、Gli1 mRNA的表达量;上调或下调EZH2表达后检测Cul4A、Gli1 m RNA的表达变化;利用免疫组化技术检测恶性胸膜间皮瘤患者病理组织中EZH2、Cul4A、Gli1表达并分析其相关性。[结果] EZH2高表达的H2452细胞中,Gli1呈高表达,而Cul4A表达量与正常细胞无明显差异,抑制EZH2表达可使Gli1表达量下降,但对Cul4A表达无明显影响。EZH2低表达的MSTO-211H细胞中,Gli1呈低表达,导入外源性EZH2基因,可使Gli1表达升高,而Cul4A表达无明显改变。恶性胸膜间皮瘤标本中,EZH2表达阳性率为77.6%(52/67),Cul4A表达阳性率为76.1%(51/67),Gli1表达阳性率为65.7%(44/67),EZH2与Gli1表达呈正相关(r=0.815,P<0.05),EZH2与Cul4A表达无明显相关性(r=0.145,P>0.05),Cul4A与Gli1表达呈正相关(r=0.577,P<0.05)。[结论]恶性胸膜间皮瘤中EZH2、Cul4A、Gli1呈高表达,并且Gli1表达与EZH2表达存在相关性,可能为EZH2的下游调控基因。[Objective] To investigate the expression of EZH2,Cul4 A and Gli1 in malignant pleural mesothelioma(MPM) and their correlations. [Methods] The expression of EZH2,Cul4 A and Gli1 m RNA in malignant mesothelioma H2452,MSTO-211 H cells and human normal mesothelial Met-5 A cells was detected by real-time RT-PCR. The expression of Cul4 A and Gli1 mRNA was also detected after up-regulating or down-regulating EZH2. The expression of EZH2,Cul4 A and Gli1 in tumor tissues was detected by immunohistochemical technique in 67 patients with MPM. The correlations among EZH2,Cul4 A and Gli1 expression were analyzed. [Results] The expression of EZH2 and Gli1 was higher in H-2452 cells,but there was no difference in Cul4 A expression compared with normal mesothelial Met-5 A cells. The expression of Gli1 was decreased,but there was no significant change in Cul4 A expression after down-regulation of EZH2 expression. The expression of EZH2 and Gli1 was both low in MSTO-211 H cells;the expression of Gli1 was increased after introduction of exogenous EZH2 gene in MSTO-211 H cells,while the expression of Cul4 A had no significant change. In malignant pleural mesothelioma tissues,the positive rate of EZH2 expression was 77.6%(52/67),Cul4 A was 76.1%(51/67),and Gli1 was 65.7%(44/67). There was a positive correlation between the expression of EZH2 and Gli1(r=0.815,P<0.05),between Cul4 A and Gli1(r=0.577,P<0.05),but no correlation between EZH2 Cul4 A expression(r=0.145,P>0.05). [Conclusion] EZH2,Cul4 A and Gli1 are highly expressed in MPM,and there is a correlation between Gli1 and EZH2 expression,indicating that Gli1 may be the downstream regulatory gene of EZH2.

关 键 词：恶性胸膜间皮瘤 EZH2 GLI1 Cul4A Hegdehog信号传导通路 

分 类 号：R734.3[医药卫生—肿瘤]