Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
Liaocheng People's Hospital, Liaocheng, Shandong 252000, P.R. China.
Int J Mol Med. 2018 Dec;42(6):3065-3072. doi: 10.3892/ijmm.2018.3869. Epub 2018 Sep 11.
Epithelial ovarian cancer (EOC) is one of the most lethal gynecological malignancies and is known to be associated with the accumulation of various genetic and epigenetic alterations. As a member of the human histone‑lysine N‑methyltransferase SETD1A (SET1)/histone‑lysine N‑methyltransferase 2A (MLL) complexes that are required for full SET1/MLL methyltransferase activity, protein dpy‑30 homolog (DPY30) catalyzes histone H3K4 methylation, and its dysfunction has been associated with the occurrence of cancer. Therefore, the present study investigated the role of DPY30 in EOC and the potential association between DPY30 expression and the clinicopathological characteristics of EOC. The expression of DPY30 was examined in EOC tissues and cell lines to identify any correlations between the clinicopathological characteristics of EOC and DPY30 expression, and to determine the effects of DPY30 on EOC cell proliferation, migration and invasion. DPY30 was highly expressed in EOC tissues and cell lines, and high DPY30 expression was significantly associated with notable clinicopathological variables in EOC patients, including International Federation of Gynecology and Obstetrics stage, pathological grade and lymph node metastasis. Functional studies on EOC cell lines demonstrated that DPY30 significantly promoted cell proliferation, migration, and invasion, accelerated cell cycle progression, and promoted epithelial‑mesenchymal transition. Chromatin immunoprecipitation assay results revealed that DPY30 regulates histone H3K4 modification via interaction with the vimentin gene promoter, suggesting that DPY30 promotes the transcription of vimentin. Finally, high expression of DPY30 was significantly associated with reduced survival in patients with EOC. The results indicated that DPY30 may act as an oncogene in EOC and thus represents a potential therapeutic target and prognostic marker in EOC.
上皮性卵巢癌（EOC）是最致命的妇科恶性肿瘤之一，已知与各种遗传和表观遗传改变的积累有关。作为人类组蛋白赖氨酸 N-甲基转移酶 SETD1A（SET1）/组蛋白赖氨酸 N-甲基转移酶 2A（MLL）复合物的成员，该复合物对于 SET1/MLL 甲基转移酶的完全活性是必需的，蛋白 dpy-30 同源物（DPY30）催化组蛋白 H3K4 甲基化，其功能障碍与癌症的发生有关。因此，本研究探讨了 DPY30 在 EOC 中的作用以及 DPY30 表达与 EOC 临床病理特征之间的潜在关联。检查了 DPY30 在 EOC 组织和细胞系中的表达，以确定 DPY30 表达与 EOC 临床病理特征之间的任何相关性，并确定 DPY30 对 EOC 细胞增殖、迁移和侵袭的影响。DPY30 在 EOC 组织和细胞系中高表达，DPY30 高表达与 EOC 患者显著的临床病理变量显著相关，包括国际妇产科联合会分期、病理分级和淋巴结转移。对 EOC 细胞系的功能研究表明，DPY30 显著促进细胞增殖、迁移和侵袭，加速细胞周期进程，并促进上皮-间充质转化。染色质免疫沉淀试验结果表明，DPY30 通过与波形蛋白基因启动子相互作用调节组蛋白 H3K4 修饰，表明 DPY30 促进波形蛋白的转录。最后，DPY30 高表达与 EOC 患者生存时间显著缩短相关。结果表明，DPY30 可能在上皮性卵巢癌中发挥癌基因的作用，因此代表上皮性卵巢癌中的一个潜在治疗靶点和预后标志物。
