Journal
EMBO JOURNAL
Volume 32, Issue 12, Pages 1665-1680Publisher
WILEY
DOI: 10.1038/emboj.2013.99
Keywords
androgen; non-coding RNA; prostate cancer
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Funding
- Grants of the Cell Innovation Program
- MEXT, Japan
- JSPS, Japan
- MHLW, Japan
- Program for Promotion of Fundamental Studies in Health Sciences, NIBIO, Japan
- Grants-in-Aid for Scientific Research [23249040, 25293214] Funding Source: KAKEN
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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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