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前列腺癌中的表观遗传编辑:挑战与机遇

Epigenetic Editing in Prostate Cancer: Challenges and Opportunities.

作者信息

Pacheco Mariana Brütt, Camilo Vânia, Henrique Rui, Jerónimo Carmen

机构信息

Cancer Biology and Epigenetics Group, Research Center (GEBC CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto) & Porto Comprehensive Cancer Center (P.CCC), R. Dr. António Bernardino de Almeida, Porto, Portugal.

Department of Pathology, Portuguese Oncology Institute of Porto (IPOP), R. DR. António Bernardino De Almeida, Porto, Portugal.

出版信息

Epigenetics. 2022 May;17(5):564-588. doi: 10.1080/15592294.2021.1939477. Epub 2021 Jun 15.

Abstract

Epigenome editing consists of fusing a predesigned DNA recognition unit to the catalytic domain of a chromatin modifying enzyme leading to the introduction or removal of an epigenetic mark at a specific locus. These platforms enabled the study of the mechanisms and roles of epigenetic changes in several research domains such as those addressing pathogenesis and progression of cancer. Despite the continued efforts required to overcome some limitations, which include specificity, off-target effects, efficacy, and longevity, these tools have been rapidly progressing and improving.Since prostate cancer is characterized by multiple genetic and epigenetic alterations that affect different signalling pathways, epigenetic editing constitutes a promising strategy to hamper cancer progression. Therefore, by modulating chromatin structure through epigenome editing, its conformation might be better understood and events that drive prostate carcinogenesis might be further unveiled.This review describes the different epigenome engineering tools, their mechanisms concerning gene's expression and regulation, highlighting the challenges and opportunities concerning prostate cancer research.

摘要

表观基因组编辑包括将预先设计的DNA识别单元与染色质修饰酶的催化结构域融合,从而在特定位点引入或去除表观遗传标记。这些平台使得在几个研究领域中能够研究表观遗传变化的机制和作用,比如那些涉及癌症发病机制和进展的领域。尽管仍需持续努力来克服一些局限性,包括特异性、脱靶效应、功效和持久性,但这些工具一直在迅速发展和改进。由于前列腺癌的特征是影响不同信号通路的多种遗传和表观遗传改变,表观遗传编辑构成了一种有前景的阻碍癌症进展的策略。因此,通过表观基因组编辑调节染色质结构,可能会更好地理解其构象,并进一步揭示驱动前列腺癌发生的事件。本综述描述了不同的表观基因组工程工具、它们关于基因表达和调控的机制,突出了前列腺癌研究面临的挑战和机遇。

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