EZH2 Contributes to Anoikis Resistance and Promotes Epithelial Ovarian Cancer Peritoneal Metastasis by Regulating m6A  

作　　者：Shao-hai WANG Lin LIU Ke-yong BAO Yi-fan ZHANG Wen-wen WANG Shi DU Na-er JIA Suo SUO Jing CAI Jian-feng GUO Gang LV 

机构地区：[1]Department of Obstetrics and Gynecology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China [2]Department of Obstetrics and Gynecology,Affiliated Hospital of Inner Mongolia University for The Nationalities,Tongliao 028000,China [3]Department of Obstetrics and Gynecology,Bozhou Branch of Union Hospital,Bozhou 833400,China [4]Department of Obstetrics and Gynecology,Bozhou People's Hospital,Bozhou 833400,China

出　　处：《Current Medical Science》2023年第4期794-802,共9页当代医学科学（英文）

基　　金：funded by the National Natural Science Foundation of China(No.81672573);Natural Science Foundation of Xinjiang Uygur Autonomous Region(No.2021D01F21);Natural Science Foundation of Hubei Province(No.2021CFB474)。

摘　　要：Objective:Histone modification has a significant effect on gene expression.Enhancer of zeste homolog 2(EZH2)contributes to the epigenetic silencing of target chromatin through its roles as a histone-lysine N-methyltransferase enzyme.The development of anoikis resistance in tumor cells is considered to be a critical step in the metastatic process of primary malignant tumors.The purpose of this study was to investigate the effect and mechanism of anoikis resistance in ovarian adenocarcinoma peritoneal metastasis.Methods:In addition to examining EZH2 protein expression in ovarian cancer omental metastatic tissues,we established a model of ovarian cancer cell anoikis and a xenograft tumor model in nude mice.Anoikis resistance and ovarian cancer progression were tested after EZH2 and N6-methyladenosine(m6A)levels were modified.Results:EZH2 expression was significantly higher in ovarian cancer omental metastatic tissues than in normal ovarian tissues.Reducing the level of EZH2 decreased the level of m6A and ovarian cancer cell anoikis resistance in vitro and inhibited ovarian cancer progression in vivo.M6a regulation altered the effect of EZH2 on anoikis resistance.Conclusion:Our results indicate that EZH2 contributes to anoikis resistance and promotes ovarian adenocarcinoma abdominal metastasis by m6A modification.Our findings imply the potential of the clinical application of m6A and EZH2 for patients with ovarian cancer.

关 键 词：ANOIKIS heterografts N6-methyladenosine enhancer of zeste homolog 2 ovarian neoplasms 

分 类 号：R737.31[医药卫生—肿瘤]