Ovarian cancer (OC) is a lethal gynecologic cancer and the common cause of death within women worldwide. The polycomb group protein enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase highly expressed in various tumors, including OC. However, the mechanistic basis of EZH2 oncogenic activity in OC remain incompletely understood. Bioinformatics analysis showed that the expression of MAPRE3 was lower in OC tissues than in normal tissues, and was positively correlated with the overall survival. MAPRE3 overexpression decreased cell growth, inducing cell cycle arrest and apoptosis in OC cells, whereas MAPRE3 silencing promoted proliferation and accelerated cell cycle progression of OC cells. The in vivo study validated that overexpression of MAPRE3 impeded tumor formation and growth of OC xenografts in nude mice. In addition, knockdown of EZH2 in OC cells downregulated H3K27me3 expression and increased MAPRE3 expression. Inhibiting EZH2 in OC cells reduced the enrichment of H3K27me3 on the promoter of MAPRE3. Furthermore, MAPRE3 silencing significantly reversed changes in the expression of cell cycle and apoptosis-related markers and cell growth mediated by EZH2 knockdown in OC cells. MAPRE3 functions as a suppressor of OC and is epigenetic repressed by EZH2, suggesting a potential therapeutic strategy for OC by targeting EZH2/MAPRE3 axis.

卵巢癌（OC）是一种致命的妇科癌症，也是全球女性死亡的常见原因。zeste 同源物 2 (EZH2) 的多梳蛋白增强子是一种组蛋白甲基转移酶，在包括 OC 在内的多种肿瘤中高度表达。然而，EZH2 在 OC 中致癌活性的机制基础仍不完全清楚。生物信息学分析显示，OC组织中MAPRE3的表达量低于正常组织，且与总生存期呈正相关。MAPRE3过表达会降低细胞生长，诱导OC细胞的细胞周期停滞和细胞凋亡，而MAPRE3沉默会促进OC细胞的增殖并加速细胞周期进程。体内研究证实，MAPRE3的过度表达可阻碍裸鼠体内OC异种移植物的肿瘤形成和生长。此外，敲低 OC 细胞中的 EZH2 会下调 H3K27me3 表达并增加 MAPRE3 表达。抑制 OC 细胞中的 EZH2 会减少 MAPRE3 启动子上 H3K27me3 的富集。此外，MAPRE3沉默显着逆转了OC细胞中EZH2敲低介导的细胞周期和凋亡相关标志物表达以及细胞生长的变化。MAPRE3 作为 OC 的抑制因子发挥作用，并且受到 EZH2 的表观遗传抑制，这表明通过靶向 EZH2/MAPRE3 轴来治疗 OC 是一种潜在的治疗策略。