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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
Wang, Sh., Liu, L., Bao, Ky. et al. EZH2 Contributes to Anoikis Resistance and Promotes Epithelial Ovarian Cancer Peritoneal Metastasis by Regulating m6A. CURR MED SCI 43, 794–802 (2023). https://doi.org/10.1007/s11596-023-2719-4
// 文章简介
在这篇由华中科技大学同济医学院附属协和医院妇产科郭剑锋教授课题组发表的研究成果中,深入探讨了增强子zeste同源物2(EZH2)在卵巢腺癌腹膜转移中的关键作用及其分子机制。研究发现,EZH2在卵巢癌腹膜转移组织中的表达显著高于正常卵巢组织,且其高表达与卵巢癌的anoikis抗性增强及腹膜转移促进密切相关。通过建立卵巢癌细胞anoikis模型和裸鼠异种移植肿瘤模型,研究人员证实了降低EZH2水平可以显著减少体外卵巢癌细胞的anoikis抗性和体内卵巢癌的进展。此外,N6-甲基腺苷(m6A)的调控在EZH2影响anoikis抗性中扮演了重要角色。本研究不仅揭示了EZH2在卵巢癌转移中的潜在机制,还为开发针对EZH2和m6A的新型治疗策略提供了科学依据,具有重要的临床应用前景。
// Abstract:
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.
ResultsEZH2 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.ConclusionOur 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.Archiver|手机版|科学网 ( 京ICP备07017567号-12 )
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