最新的研究表明TET1介导5甲基-胞嘧啶的羟甲基化修饰可以改变基因组甲基化谱，影响大量下游基因的转录调控，决定细胞分化方向与生物学行为。我们的前期工作表明，在前列腺癌细胞及组织中TET1表达水平远低于正常前列腺细胞系及癌旁组织。通过最新的文献分析我们发现TET1通过MBD3/NuRD/LSD1复合体调控下游基因，且已有研究证明LSD1与AR互为受体-配体关系，而是否TET1可通过AR调控下游基因表达尚未阐明。本课题将研究TET1与AR之间的相互作用对去势抵抗性前列腺癌（CRPC）的影响，通过在细胞水平调控TET1的表达，发现其主要影响的靶基因，随后在动物荷瘤模型中加以验证。最后将在组织标本水平探讨TET1与AR共同调控的靶基因对CRPC的作用，为临床应用提供有力依据。本研究有助于揭示前列腺癌发生的羟甲基化调控机制及受其调控的基因，为CRPC的治疗提供崭新的思路。

Recently studies demonstrated that TET1 mediated DNA hydroxymethylation could modify the DNA methylome, which is crucially important. TET1 can turn on or off gene transcription that matters a lot in cell differentiation by modificating methylated DNA into hydromethylated. Our previous research established that TET1 protein level decreased in prostate cancer tissues and cells than adjacent tissues and normal prostate cell line RWPE-1. Latest study proved that TET1 participate MBD3/NuRD/LSD1 complex to regulate downstream gene expression. Intersting is LSD1 and AR interact as ligand and receptor. But the way how AR and TET1 interact is still unknown. Our study aims to elucidate the interaction of AR and TET1 on castration resistant prostate cancer(CRPC) and find out the regulated genes of TET1 in vitro and validate them in vivo. We will test the effect on CRPC of TET1 and AR co-regulated genes in clinical cohorts to provide evidence for clinical practise. Our project may help our understanding of the underlying mechanism of DNA droxymethylation regulated gene expression in prostate cancer progression. It provides new approaches for the prevention and management of prostate cancer.