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

Ken-ichi Takayama, Aya Misawa, Takashi Suzuki, Kiyoshi Takagi, Yoshihide Hayashizaki, Tetsuya Fujimura, Yukio Homma, Satoru Takahashi, Tomohiko Urano and Satoshi Inoue ()
Additional contact information
Ken-ichi Takayama: Graduate School of Medicine, The University of Tokyo
Aya Misawa: Graduate School of Medicine, The University of Tokyo
Takashi Suzuki: Graduate School of Medicine, Tohoku University
Kiyoshi Takagi: Graduate School of Medicine, Tohoku University
Yoshihide Hayashizaki: RIKEN Omics Science Center (OSC), RIKEN Yokohama Institute
Tetsuya Fujimura: Graduate School of Medicine, The University of Tokyo
Yukio Homma: Graduate School of Medicine, The University of Tokyo
Satoru Takahashi: Nihon University School of Medicine
Tomohiko Urano: Graduate School of Medicine, The University of Tokyo
Satoshi Inoue: Graduate School of Medicine, The University of Tokyo

Nature Communications, 2015, vol. 6, issue 1, 1-16

Abstract: 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.

Date: 2015
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms9219 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9219

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms9219

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().