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TET2 repression by androgen hormone regulates global hydroxymethylation status and prostate cancer progression.

Abstract：

:Modulation of epigenetic patterns has promising efficacy for treating cancer. 5-Hydroxymethylated cytosine (5-hmC) is an epigenetic mark potentially important in cancer. Here we report that 5-hmC is an epigenetic hallmark of prostate cancer (PCa) progression. A member of the ten-eleven translocation (TET) proteins, which catalyse the oxidation of methylated cytosine (5-mC) to 5-hmC, TET2, is repressed by androgens in PCa. Androgen receptor (AR)-mediated induction of the miR-29 family, which targets TET2, are markedly enhanced in hormone refractory PCa (HRPC) and its high expression predicts poor outcome of PCa patients. Furthermore, decreased expression of miR-29b results in reduced tumour growth and increased TET2 expression in an animal model of HRPC. Interestingly, global 5-hmC modification regulated by miR-29b represses FOXA1 activity. A reduction in 5-hmC activates PCa-related key pathways such as mTOR and AR. Thus, DNA modification directly links the TET2-dependent epigenetic pathway regulated by AR to 5-hmC-mediated tumour progression.

journal_name

Nat Commun

journal_title

Nature communications

authors

Takayama K,Misawa A,Suzuki T,Takagi K,Hayashizaki Y,Fujimura T,Homma Y,Takahashi S,Urano T,Inoue S

doi

10.1038/ncomms9219

subject

Has Abstract

pub_date

2015-09-25 00:00:00

pages

8219

issn

2041-1723

pii

ncomms9219

journal_volume

6

pub_type

杂志文章

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