Departments of, Department of, Urology, Chiba University Graduate School of Medicine, Chiba, Japan.
Department of, Molecular Oncology, Chiba University Graduate School of Medicine, Chiba, Japan.
Int J Urol. 2021 Feb;28(2):140-149. doi: 10.1111/iju.14406. Epub 2020 Oct 27.
Prostate cancer is a major cause of cancer-related deaths among men worldwide. In addition to genomic alterations, epigenetic alterations accumulated in prostate cancer have been elucidated. While aberrant deoxyribonucleic acid hypermethylation in promoter CpG islands inactivates crucial genes associated with deoxyribonucleic acid repair, cell cycle, apoptosis or cell adhesion, aberrant deoxyribonucleic acid hypomethylation can lead to oncogene activation. Acetylation of histone is also deregulated in prostate cancer, which could cause aberrant super-enhancer formation and activation of genes associated with cancer development. Deregulations of histone methylation, such as an increase of trimethylation at position 27 of histone H3 by enhancer of zeste homolog2 overexpression, or other modifications, such as phosphorylation and ubiquitination, are also involved in prostate cancer development, and inhibitors targeting these epigenomic aberrations might be novel therapeutic strategies. In this review, we provide an overview of epigenetic alterations in the development and progression of prostate cancer, focusing on deoxyribonucleic acid methylation and histone modifications.
前列腺癌是全球男性癌症相关死亡的主要原因之一。除了基因组改变外，在前列腺癌中积累的表观遗传改变也已经阐明。虽然启动子 CpG 岛上的异常脱氧核糖核酸超甲基化使与脱氧核糖核酸修复、细胞周期、细胞凋亡或细胞黏附相关的关键基因失活，但异常脱氧核糖核酸低甲基化可导致癌基因激活。组蛋白的乙酰化在前列腺癌中也失调，这可能导致异常超级增强子的形成和与癌症发展相关基因的激活。组蛋白甲基化的失调，如增强子结合蛋白 2 过表达导致组蛋白 H3 第 27 位三甲基化增加，或其他修饰，如磷酸化和泛素化，也参与了前列腺癌的发展，针对这些表观遗传异常的抑制剂可能是新的治疗策略。在这篇综述中，我们提供了前列腺癌发展和进展中表观遗传改变的概述，重点关注脱氧核糖核酸甲基化和组蛋白修饰。
