Epigenetic Editing in Prostate Cancer: Challenges and Opportunities

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.

Keywords: Prostate cancer; crispr-dCas9; epigenome editing; fusion proteins.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CRISPR-Cas Systems
  • Chromatin
  • DNA Methylation
  • Epigenesis, Genetic
  • Gene Editing*
  • Humans
  • Male
  • Prostatic Neoplasms* / genetics

Substances

  • Chromatin

Grants and funding

CJ research is supported by Programa Operacional Competitividade e Internacionalização (POCI), in the component FEDER, and by national funds (OE) through FCT/MCTES, in the scope of the project HyTherCaP- POCI-01-0145-FEDER-29030 (PTDC/MECONC/29030/2017). The HyTherCaP project is also acknowledged for VC Junior Researcher position. MBP was supported by a fellowship from Liga Portuguesa Contra o Cancro-Núcleo Regional do Norte.