EZH2调控卵巢癌细胞生物学行为的机制研究  

Investigation on the mechanism of EZH2 regulating biological behavior of ovarian cancer cells

作　　者：朱玲[1,2] 王科 赵峰 李思齐 王书奎 邵启祥[2,3] ZHU Ling;WANG Ke;ZHAO Feng;LI Siqi;WANG Shukui;SHAO Qixiang(Department of Laboratory Medicine,Nanjing First Hospital,Nanjing Medical University,Nanjing 210006,Jiangsu;Institute of Medical Genetics and Reproductive Immunity,the Digestive and Reproductive System Cancers Precise Prevention Engineering Research Center of Jiangsu Province,Jiangsu College of Nurs-ing,Huai′an 223005,Jiangsu;School of Medicine,Jiangsu University,Zhenjiang 212013,Jiangsu,China)

机构地区：[1]南京医科大学附属南京医院检验科,南京210006 [2]江苏护理职业学院江苏省消化及生殖系统肿瘤精准防治工程研究中心医学遗传与生殖免疫研究所,江苏淮安223005 [3]江苏大学医学院,江苏镇江212013

出　　处：《临床检验杂志》2024年第7期542-547,共6页Chinese Journal of Clinical Laboratory Science

基　　金：江苏护理职业学院创新团队(SHCXTD 2023052901);江苏护理职业学院领军人才项目(2021L001);江苏省自然基金面上项目(BK20231236)。

摘　　要：目的探讨组蛋白甲基化转移酶Zeste同源物增强子2(enhancer of zeste homolog 2,EZH2)调控卵巢癌(ovarian cancer,OC)生物学行为的机制,为寻找OC治疗的新靶点提供实验支持。方法采用EZH2小干扰RNA(small interfered RNA,siRNA)在不同OC细胞系中敲减EZH2,并使用qRT-PCR、Western blot分析干扰siEZH2 mRNA和蛋白质的效率。进一步采用CCK-8法、细胞划痕试验、Transwell试验以及流式细胞术检测干扰EZH2后对OC细胞增殖、迁移及侵袭能力和凋亡水平等生物学行为的影响。采用Western blot分析干扰EZH2后,早期生长反应因子1(early growth response 1,EGR1)和H3K27me3蛋白的表达水平,并分析EZH2调控OC细胞生物学行为的机制。结果转染siEZH2后,OC细胞系中EZH2 mRNA的表达水平显著低于阴性对照组,差异有统计学意义(P<0.05),且A2780细胞中EZH2蛋白的表达水平亦明显下调(P<0.05)。Western blot检测结果表明,EGR1以及H3K27me3蛋白水平出现了不同程度地降低。转染siEZH2-1后,转染组A2780细胞的增殖能力显著低于阴性对照组(P<0.05);细胞划痕试验和Transwell试验结果显示,转染siEZH2-1后细胞的迁移和侵袭能力显著减弱(P<0.05);流式细胞术结果显示,转染siEZH2-1后细胞凋亡水平显著增强(P<0.05)。结论EZH2在OC细胞系中高表达,并促进A2780细胞的增殖、迁移、侵袭和抗凋亡。但EZH2并非通过其H3K27me3转移酶功能调控EGR1的表达而调控影响OC的生物学行为。Objective To investigate the mechanism of enhancer of zeste homolog 2(EZH2),a histone methyltransferase,in regula-ting the biological behavior of ovarian cancer(OC)and provide the experimental support for finding new therapeutic targets in the treat-ment of OC.Methods The small interfered RNAs(siRNAs)of EZH2 were used to knock down EZH2 in different OC cell lines,and the interfering efficiency of siEZH2 mRNAs and protein were evaluated by qRT-PCR and Western blot.The cell proliferation,migra-tion,invasion ability and apoptosis of OC cells before and after EZH2 interference were evaluated by the CCK-8,wound healing,Tran-swell and flow cytometry.The expression levels of early growth response 1(EGR1)and H3K27me3 proteins after EZH2 interference were determined by Western blot.Meanwhile,the mechanism of EZH2 regulating the biological behavior of OC cells was explored.Re-sults The expression levels of EZH2 mRNA in OC cells transfected with siEZH2 were significantly lower than that in the negative con-trol group(P<0.05)and the expression levels of EZH2 protein in A2780 cells were also significantly downregulated(P<0.05).The results of Western blot showed that the expression levels of EGR1 and H3K27me3 proteins were reduced to varying degrees.After trans-fection with siEZH2-1,the proliferation ability of A2780 cells in the transfected group was significantly lower than that in the negative control group(P<0.05).The results of the cell scratch test and Transwell test showed that the migration and invasion ability of OC cells transfected with siEZH2-1 were significantly weakened(P<0.05).The results of flow cytometry showed that the apoptosis of OC cells transfected with siEZH2-1 was significantly enhanced(P<0.05).Conclusion EZH2 is highly expressed in OC cells and can promote the proliferation,migration,invasion and anti-apoptosis of A2780 cells.However,EZH2 affects the biological behavior of ovar-ian cancer not by regulating the expression of EGR1 through its H3K27me3 transferase activity.

关 键 词：卵巢癌 组蛋白甲基化转移酶Zeste同源物增强子2 早期生长反应因子1 

分 类 号：R446[医药卫生—诊断学]