Department of Anti-Aging Medicine, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
EMBO J. 2013 Jun 12;32(12):1665-80. doi: 10.1038/emboj.2013.99. Epub 2013 May 3.
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.
高通量技术已经鉴定出许多反义(AS)转录本和长非编码 RNA(ncRNA)。然而,它们在癌症生物学中的意义在很大程度上仍然未知。在这里,我们报告了一种雄激素反应性长 ncRNA,CTBP1-AS,位于 C 端结合蛋白 1(CTBP1)的 AS 区域,CTBP1 是雄激素受体的核心抑制剂。CTBP1-AS 主要定位于细胞核,其表达在前列腺癌中普遍上调。CTBP1-AS 促进激素依赖性和去势抵抗性肿瘤的生长。在机制上,CTBP1-AS 通过与组蛋白去乙酰化酶一起募集 RNA 结合转录抑制因子 PSF,直接抑制 CTBP1 的表达。CTBP1-AS 还通过 PSF 依赖性机制抑制肿瘤抑制基因,从而促进细胞周期进程,表现出全局雄激素依赖性功能。我们的研究结果为直接促进前列腺癌进展的 ncRNA 的功能提供了新的见解。