Green Templeton College, University of Oxford, Oxford, OX2 6HG, UK.
Surgery, Women's and Oncology Division, John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, OX3 9DU, UK.
Epigenomics. 2022 Jun;14(11):699-709. doi: 10.2217/epi-2021-0534. Epub 2022 May 16.
Cancer epigenetic mechanisms support the acquisition of hallmark characteristics during oncogenesis. EZH2 - an important histone methyltransferase that writes histone H3 lysine 27 trimethylation marks - is known to be dysregulated in cancer cells. However, the interactions between EZH2 and miRNAs that form a complex network of cross-talk and reciprocal regulation that enable cancer cells to acquire hallmark characteristics have been relatively poorly appreciated. The specific functions of EZH2 appear to be regulated by a vast array of miRNAs, which direct EZH2 toward regulation over the development of specific hallmark characteristics. This review discusses recent advances in the understanding of EZH2, focusing on its collaboration with miRNAs to orchestrate oncogenesis. These epigenetic processes promote the evasion of apoptosis/cell cycle arrest, cellular dedifferentiation and the establishment of a tumor microenvironment that facilitates local cancer cell invasion, anti-cancer drug resistance and evasion of the immune response.
癌症表观遗传机制支持肿瘤发生过程中标志性特征的获得。EZH2 是一种重要的组蛋白甲基转移酶，它在组蛋白 H3 赖氨酸 27 位上进行三甲基化标记，已知在癌细胞中失调。然而，EZH2 与 miRNAs 之间的相互作用形成了一个复杂的交叉对话和相互调节的网络，使癌细胞获得标志性特征，这方面的认识相对较差。EZH2 的特定功能似乎受到大量 miRNAs 的调节，这些 miRNAs 指导 EZH2 调节特定标志性特征的发育。这篇综述讨论了对 EZH2 理解的最新进展，重点讨论了它与 miRNAs 的协作，以协调肿瘤发生。这些表观遗传过程促进了细胞凋亡/细胞周期阻滞的逃逸、细胞去分化以及肿瘤微环境的建立，这有利于局部癌细胞的侵袭、抗癌药物耐药性和免疫反应的逃避。
