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

雄激素反应性长链非编码RNA CTBP1-AS促进前列腺癌

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作者: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

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.

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