药物靶点的发现和验证是新药研究源头创新的基础，孤儿G蛋白偶联受体是药物新靶点的重要来源。前列腺癌是一种严重的男性老年疾病，迫切需要新的作用机制的药物研发。我们的前期研究发现孤儿G蛋白偶联受体GPR160在前列腺癌细胞和组织中高表达，对其基因敲除可诱导前列腺癌细胞程序性死亡，同时伴有caspase-1表达上调。因caspase-1的表达上调与细胞炎症反应和细胞焦亡（pyroptosis）密切相关，本项目拟深入研究：1）临床前列腺炎和前列腺癌组织中GPR160的表达差异；2）促炎症信号刺激下GPR160的表达变化；3）GPR160对细胞焦亡的调节及其分子机制；4）GPR160小分子调节剂的筛选及其对前列腺癌细胞生长和焦亡的影响。本项目的研究将为研发具有全新作用机制的抗前列腺癌药物提供新靶点和实验依据。

The discovery and validation of drug targets is important for the innovation of drug research. Orphan G protein-coupled receptors are the major source of novel drug target. Prostate cancer is a serious disease of elderly men which has an urgent need in the market for the drug discovery with a new molecular mechanism. In our previous study, we have found that the expression of orphan G protein-coupled receptor, GPR160, was significantly higher in prostate cancer tissue samples and cells than that of normal. Gene silencing of endogenous GPR160 resulted in programmed cell death together with an increase of caspase-1 expression, which played a key role in pyroptotic cell death. This study will evaluate the correlation between the expression level of GPR160 and the pathogenesis of prostate cancer. The change of GPR160 expression in tissue samples from prostatitis and prostate cancer patients will be assessed. Under the stimulation of proinflammatory factors the effects of GPR160 expression on the proliferation, invasion, apoptosis and pyroptosis of prostate cancer cells will be studied and the related molecular mechanism will be elucidated. A high-throughput screening for small molecule GPR160 agonists and antagonists will be carried out. This study aims to provide a new target and experimental basis for the development of anti-prostate cancer drugs with novel mechanisms.