EZH2 in Bladder Cancer, a Promising Therapeutic Target

Int J Mol Sci. 2015 Nov 13;16(11):27107-32. doi: 10.3390/ijms161126000.

Abstract

Bladder Cancer (BC) represents a current clinical and social challenge. The recent studies aimed to describe the genomic landscape of BC have underscored the relevance of epigenetic alterations in the pathogenesis of these tumors. Among the epigenetic alterations, histone modifications occupied a central role not only in cancer, but also in normal organism homeostasis and development. EZH2 (Enhancer of Zeste Homolog 2) belongs to the Polycomb repressive complex 2 as its catalytic subunit, which through the trimethylation of H3 (Histone 3) on K27 (Lysine 27), produces gene silencing. EZH2 is frequently overexpressed in multiple tumor types, including BC, and plays multiple roles besides the well-recognized histone mark generation. In this review, we summarize the present knowledge on the oncogenic roles of EZH2 and its potential use as a therapeutic target, with special emphasis on BC pathogenesis and management.

Keywords: EZH2; Polycomb; bladder cancer; lncRNA; miRNA.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • DNA Methylation
  • Enhancer of Zeste Homolog 2 Protein
  • Epigenesis, Genetic
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing
  • Histones / metabolism
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Molecular Targeted Therapy
  • Polycomb Repressive Complex 2 / antagonists & inhibitors
  • Polycomb Repressive Complex 2 / genetics*
  • Polycomb Repressive Complex 2 / metabolism*
  • Protein Binding
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism
  • Urinary Bladder Neoplasms / drug therapy
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / metabolism*

Substances

  • Antineoplastic Agents
  • Histones
  • MicroRNAs
  • RNA, Long Noncoding
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Polycomb Repressive Complex 2