摘要
Changes in epigenetic programming are associated with cancer development during childhood. Components of the epigenetic machinery involved in normal embryonic development and hijacked by pediatric cancers include enzymes mediating post-translational modifications of DNA and histones that regulate chromatin structure, such as histone methyltransferases (HMTs). Overexpression of the HMT G9a (euchromatic histone lysine methyltransferase 2, EHMT2) has been described in several cancer types. Medulloblastoma (MB), the main type of malignant brain tumor afflicting children, is currently classified into four molecular subgroups. Here, we show that expression level of the G9a/Ehmt2 gene is higher in MB tumors belonging to the SHH, Group 3, and Group 4 subgroups, compared to Wnt tumors. Remarkably, high G9a expression was significantly associated with shorter overall survival in MB patients. We also present evidence that G9a inhibition dose-dependently reduces MB cell viability. Our findings suggest that higher transcription of G9a may be a predictor of poor prognosis in patients with SHH MB, and that inhibiting G9a activity can display antitumor effects in MB.
摘要译文
表观遗传编程的变化与儿童期癌症的发展有关。参与正常胚胎发育和被小儿癌劫持的表观遗传机制的成分包括介导DNA和组蛋白的翻译后修饰的酶，这些酶调节染色质结构，例如组蛋白甲基转移酶（HMTS）。在几种癌症类型中已经描述了HMT G9A（光蛋白赖氨酸甲基转移酶2，EHMT2）的过表达。甲状腺母细胞瘤（MB）是患有恶性脑肿瘤儿童的主要类型，目前已分为四个分子亚组。在这里，我们表明与WNT肿瘤相比，属于SHH，3组和4组亚组的MB肿瘤中G9A/EHMT2基因的表达水平更高。值得注意的是，高G9A表达与MB患者的总体生存率较短显着相关。我们还提供了证据，表明G9A抑制剂量依赖性地降低了MB细胞活力。我们的发现表明，G9A的更高转录可能是SHH MB患者预后不良的预测指标，并且抑制G9A活性会在MB中表现出抗肿瘤作用。
Souza; Barbara Kunzler[1];Freire; Natalia Hogetop[1];Jaeger; Mariane[1];de Farias; Caroline Brunetto[1];Brunetto; Algemir L.[1];Brunetto; André T.[1];Roesler; Rafael[1]. G9a/EHMT2 is a Potential Prognostic Biomarker and Molecular Target in SHH Medulloblastoma[J]. NeuroMolecular Medicine, 2022,24(4): 392-398