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

我们在ctbp1 （Carboxyl terminal binding protein 1）的反义区发现了一个长链非编码RNA，并将其命名为“ctbp1 - as”。CTBP1- as由雄激素诱导，抑制CTBP1。前列腺癌中CTBP1-AS的上调促进激素依赖性和去势抵抗性肿瘤的生长。此外，我们还证明了CTBP1-AS与一个具有rna结合结构域的表观遗传修饰子的相互作用，然后在全基因组范围内调控基因表达。有趣的是，细胞周期调控因子在这些调控基因中显著富集。综上所述，我们证明了一种新的激素依赖性细胞周期调节机制，CTBP1-AS可能是激素难治性前列腺癌的治疗靶点。我们还鉴定并分析了雄激素调节的mirna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、抗比卡鲁胺的细胞增殖有关。我们将通过异种移植模型实验来揭示激素难治性前列腺癌的发生机制。

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.