Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre 90035-003, Brazil.
Epigenica Biosciences, Canoas 92035-000, Brazil.
Int J Mol Sci. 2021 Oct 19;22(20):11292. doi: 10.3390/ijms222011292.
Epigenetic mechanisms, including post-translational modifications of DNA and histones that influence chromatin structure, regulate gene expression during normal development and are also involved in carcinogenesis and cancer progression. The histone methyltransferase G9a (euchromatic histone lysine methyltransferase 2, EHMT2), which mostly mediates mono- and dimethylation by histone H3 lysine 9 (H3K9), influences gene expression involved in embryonic development and tissue differentiation. Overexpression of G9a has been observed in several cancer types, and different classes of G9a inhibitors have been developed as potential anticancer agents. Here, we review the emerging evidence suggesting the involvement of changes in G9a activity in brain tumors, namely glioblastoma (GBM), the main type of primary malignant brain cancer in adults, and medulloblastoma (MB), the most common type of malignant brain cancer in children. We also discuss the role of G9a in neuroblastoma (NB) and the drug development of G9a inhibitors.
表观遗传机制，包括影响染色质结构的 DNA 和组蛋白的翻译后修饰，在正常发育过程中调节基因表达，也参与癌发生和癌症进展。组蛋白甲基转移酶 G9a（常染色质组蛋白赖氨酸甲基转移酶 2，EHMT2）主要通过组蛋白 H3 赖氨酸 9（H3K9）介导单甲基化和二甲基化，影响胚胎发育和组织分化过程中涉及的基因表达。在几种癌症类型中观察到 G9a 的过表达，并且已经开发出不同类别的 G9a 抑制剂作为潜在的抗癌药物。在这里，我们回顾了越来越多的证据表明 G9a 活性的变化参与了脑肿瘤，即神经胶质瘤（GBM），成人原发性恶性脑癌的主要类型，以及髓母细胞瘤（MB），儿童最常见的恶性脑癌。我们还讨论了 G9a 在神经母细胞瘤（NB）中的作用以及 G9a 抑制剂的药物开发。
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