Identification and functional analysis of androgen-responsive ncRNAs in prostate cancer

我们在CTBP 1（CarboxylTerminalBindingProtein 1）的反义区域发现了一个长的非编码RNA，并将其命名为CTBP 1-AS。CTBP 1-AS由雄激素处理诱导并抑制CTBP 1。前列腺癌中CTBP 1-AS的上调促进了去势依赖性和去势抵抗性肿瘤生长此外，我们还证明了CTBP 1-AS与一种具有RNA结合结构域的表观遗传修饰剂的相互作用，然后对基因表达进行全基因组调控。有趣的是，细胞周期调节因子在这些受调节的基因中显著富集。综上所述，我们证实了一种新的激素依赖性细胞周期调控机制，CTBP 1-AS可能成为激素难治性前列腺癌的治疗靶点，并鉴定和分析了雄激素调节的miRNAs的功能。我们发现其中一种miRNA促进前列腺癌的生长，并与抗雄激素、比卡鲁胺耐药细胞的增殖有关。我们将进行异种移植模型的实验，以显示难治性前列腺癌的发展机制。

We have identified a long non-coding RNA, which is located at the antisense region ofCTBP1 (Carboxyl teiminal binding protein 1) and then named this transcript‘CTBP1-AS’. CTBP1-AS is induced by androgen treatment and represses CTBP1. Upregulation of CTBP1-AS in prostate cancer promotes hormone-dependent and castration-resistant tumor growth. In addition, we also demonstrated the interaction of CTBP1-AS with one of the epigenetic modifiers which has RNA-binding domains and then subsequent genome-wide regulation of gene expression. Interestingly, cell cycle regulators are significantly enriched in such regulated genes. Taken together, we demonstrated a novel hormone dependent cell cycle regulation mechanism and CTBP1-AS may be a therapeutic targets for hormone refractory prostate cancer.We also identified and analyzed the functions of androgen-regulated miRNAs. We found one of such miRNA promotes prostate cancer growth and is related with the anti-androgen, bicalutamide-resistant cell proliferation. We are going to perform experiments of xenograft model to show the mechanism of development of hormonerefractory prostate cancer.