Androgen-responsive long noncoding RNA CTBP1-AS promotes prostate cancer

Ken Ichi Takayama, Kuniko Horie-Inoue, Shintaro Katayama, Takashi Suzuki, Shuichi Tsutsumi, Kazuhiro Ikeda, Tomohiko Urano, Tetsuya Fujimura, Kiyoshi Takagi, Satoru Takahashi, Yukio Homma, Yasuyoshi Ouchi, Hiroyuki Aburatani, Yoshihide Hayashizaki, Satoshi Inoue

Research output: Contribution to journalArticlepeer-review

196 Citations (Scopus)

Abstract

High-throughput techniques have identified numerous antisense (AS) transcripts and long non-coding RNAs (ncRNAs). However, their significance in cancer biology remains largely unknown. Here, we report an androgen-responsive long ncRNA, CTBP1-AS, located in the AS region of C-terminal binding protein 1 (CTBP1), which is a corepressor for androgen receptor. CTBP1-AS is predominantly localized in the nucleus and its expression is generally upregulated in prostate cancer. CTBP1-AS promotes both hormone-dependent and castration-resistant tumour growth. Mechanistically, CTBP1-AS directly represses CTBP1 expression by recruiting the RNA-binding transcriptional repressor PSF together with histone deacetylases. CTBP1-AS also exhibits global androgen-dependent functions by inhibiting tumour-suppressor genes via the PSF-dependent mechanism thus promoting cell cycle progression. Our findings provide new insights into the functions of ncRNAs that directly contribute to prostate cancer progression.

Original languageEnglish
Pages (from-to)1665-1680
Number of pages16
JournalEMBO Journal
Volume32
Issue number12
DOIs
Publication statusPublished - 2013 Jun 12

Keywords

  • androgen
  • non-coding RNA
  • prostate cancer

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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