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

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 man

SUBMITTER: Yi Y 

PROVIDER: S-EPMC9097394 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature