PPARγ在膀胱癌中高表达且过度激活，但直接打靶PPARγ有极强的副作用，因此寻找调节PPARγ转录后修饰相关蛋白能为选择性打靶PPARγ提供新的策略。前期的筛选提示PPARγ可能是UCHL3的底物，在膀胱癌中UCHL3与PPARγ密切相关且促进膀胱癌生长增殖及迁移，另一方面过表达PPARγ能上调UCHL3转录水平。基于此我们提出假说：UCHL3通过去泛素化增加PPARγ稳定性且UCHL3-PPARγ形成正反馈环，进一步放大PPARγ信号转导，促进膀胱癌发生。本项目拟: 1.在体外内外验证UCHL3在肿瘤中的功能及是否其通过PPARγ促进了肿瘤发生；2.确定PPARγ是UCHL3的底物；3.明确UCHL3-PPARγ反馈环之间的分子调控机制。本研究将揭示UCHL3-PPARγ反馈环在膀胱癌发病机制中的作用，为早期诊断、靶向治疗及预后判断提供重要的理论依据。

PPARγ is highly expressed and over-activated in bladder cancer. Direct targeting of PPARγ has strong side effects. Therefore, finding a regulatory gene for PPARγ post-transcription modification can provide a new strategy for selective targeting of PPARγ. Our previous study suggests that PPARγ may be a substrate for UCHL3. UCHL3, which is highly expressed in bladder cancer, is closely related to PPARγ and promotes the growth and migration of bladder cancer, on the other hand, overexpression of PPARγ upregulated transcription level of UCHL3. Based on this, we proposed hypothesis: UCHL3 increases PPARγ stability by deubiquitination and UCHL3-PPARγ forms a positive feedback loop, further amplifying the PPARγ signaling, leading to bladder cancer. This project is intended to: 1. Verify the function of UCHL3 in tumors in vitro and in patients and whether it regulates tumorigenesis through PPARγ; 2. Identify PPARγ is the substrate of UCHL3; 3. Identify the molecular regulation mechanism between UCHL3-PPARγ feedback loops. This study will reveal the role of UCHL3-PPARγ feedback loop in the pathogenesis of bladder cancer, providing an important theoretical basis for early diagnosis, targeted therapy and prognosis.