前列腺癌是泌尿生殖系统常见肿瘤之一，近年来在我国发病率呈明显上升趋势。雄激素受体AR作为转录因子调控下游靶基因表达，在前列腺癌发生进展中起到重要作用，为内分泌治疗的分子基础，然而以雄激素或者雄激素与其受体之间相互作用为靶点的ADT治疗最终失败，因此寻找抑制雄激素受体通路而与激活配体无关的方案依然是前列腺癌治疗的难点。我们近期发现：腺病毒12型E1A (E1A12) CR3结构域与AR NTD相互作用并抑制AR NTD转录激活功能和前列腺癌细胞增殖，E1A12介导AR雄激素非依赖性细胞核转移，然而具体分子机制尚不清楚。本研究旨在探讨E1A12 CR3与AR NTD相互作用及E1A12促进AR雄激素非依赖性细胞核转移的分子机制，阐述E1A12抑制AR转录激活功能的生物学机制，明确E1A12通过AR靶基因和下游信号通路对前列腺癌细胞生物学行为的影响，所获结果将为前列腺癌治疗提供依据和新思路。

Prostate cancer is one of the most common malignancies of the genitourinary system. In recent years, the incidence of prostate cancer tends to be an upward trend in China. Androgen receptor (AR), a well-known transcription factor, plays an important role in the occurrence and progression of prostate cancer by regulating its downstream genes, which is the molecular basis of the endocrine therapy. However, the ADT targeting either androgen or the interaction between AR and its ligand will finally fail. Therefore, screening the ideal way to inhibit AR activity in prostate cancer independent of ligand is still a difficult field. Recent studies in our group preliminarily confirmed that the CR3 region of the type 12 adenovirus E1A (E1A12) interacted directly with AR NTD and inhibited the transcriptional activation of AR NTD as well as the proliferation of prostate cancer. Still, E1A12 significantly promoted the nuclear translocation of AR independent of androgen. However, the mechanism is still unknown. In this project, we intend to thoroughly investigate the specific mechanisms of the interaction between E1A12 CR3 and AR NTD. Then, we will clarify molecular mechanisms of E1A12-mediated the nuclear translocation of AR in an androgen-independent mode. In addition, we will elaborate the biological mechanisms of E1A12 inhibiting the transcriptional activation function of AR. And so forth, we will specifically study the target genes and downstream signaling pathways of AR through which E1A12 affects the biological behavior of prostate cancer. The obtained achievements will provide a theoretical basis and new ideas for prostate cancer therapy.