Methylation-dependent and -independent roles of EZH2 synergize in CDCA8 activation in prostate cancer

Yang Yi, Yanqiang Li, Chao Li, Longxiang Wu, Dongyu Zhao, Fuxi Li, Ladan Fazli, Rui Wang, Long Wang, Xuesen Dong, Wei Zhao, Kaifu Chen, Qi Cao

Research output: Contribution to journalArticlepeer-review

Abstract

Cell division cycle-associated 8 (CDCA8) is a component of chromosomal passenger complex (CPC) that participates in mitotic regulation. Although cancer-related CDCA8 hyperactivation has been widely observed, its molecular mechanism remains elusive. Here, we report that CDCA8 overexpression maintains tumorigenicity and is associated with poor clinical outcome in patients with prostate cancer (PCa). Notably, enhancer of zeste homolog 2 (EZH2) is identified to be responsible for CDCA8 activation in PCa. Genome-wide assays revealed that EZH2-induced H3K27 trimethylation represses let-7b expression and thus protects the let-7b-targeting CDCA8 transcripts. More importantly, EZH2 facilitates the self-activation of E2F1 by recruiting E2F1 to its own promoter region in a methylation-independent manner. The high level of E2F1 further promotes transcription of CDCA8 along with the other CPC subunits. Taken together, our study suggests that EZH2-mediated cell cycle regulation in PCa relies on both its methyltransferase and non-methyltransferase activities.

Original languageEnglish (US)
Pages (from-to)1610-1621
Number of pages12
JournalOncogene
Volume41
Issue number11
DOIs
StatePublished - Mar 10 2022

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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