PDF(Pubmed)
Abstract：
Changes in epigenetic programming have been proposed as being key events in the initiation and progression of childhood cancers. HMT euchromatic histone lysine methyltransferase 2 (G9a, EHMT2), which is encoded by the G9a (Ehmt2) gene, as well as its related protein GLP, which is encoded by the GLP/Ehmt1 gene, participate in epigenetic regulation by contributing to a transcriptionally repressed chromatin state. G9a/GLP activation has been reported in several cancer types. Herein, we evaluated the role of G9a in two solid pediatric tumors: neuroblastoma (NB) and Ewing sarcoma (ES). Our results show that G9a/Ehmt2 and GLP/Ehmt1 expression is higher in tumors with poorer prognosis, including St4 International Neuroblastoma Staging System (INSS) stage, MYCN amplified NB, and metastatic ES. Importantly, higher G9a and GLP levels were associated with shorter patient overall survival (OS) in both NB and ES. Moreover, pharmacological inhibition of G9a/GLP reduced cell viability in NB and ES cells. These findings suggest that G9a and GLP are associated with more aggressive NB and ES tumors and should be further investigated as being epigenetic targets in pediatric solid cancers.
摘要：
表观遗传编程的变化已被认为是儿童癌症发生和发展的关键事件。HMT原色组蛋白赖氨酸甲基转移酶2(G9a，EHMT2),由G9a（Ehmt2）基因编码，以及它的相关蛋白GLP，由GLP/Ehmt1基因编码，通过促进转录抑制的染色质状态参与表观遗传调控。已经报道了G9a/GLP激活在几种癌症类型中。在这里，我们评估了G9a在两种实体儿科肿瘤中的作用:神经母细胞瘤(NB)和尤因肉瘤(ES).我们的结果表明，G9a/Ehmt2和GLP/Ehmt1在预后较差的肿瘤中表达更高，包括St4国际神经母细胞瘤分期系统（INSS）阶段，MYCN扩增NB,和转移性ES。重要的是,在NB和ES中,较高的G9a和GLP水平与较短的患者总生存期(OS)相关.此外，G9a/GLP的药理学抑制降低了NB和ES细胞中的细胞活力。这些发现表明G9a和GLP与更具侵袭性的NB和ES肿瘤相关，应作为儿科实体癌的表观遗传靶标进行进一步研究。
