膀胱癌的诊断和治疗数十年来缺乏技术进展和革新，患者的生存期无明显延长。多项新近研究揭示FGFR3及其激活的MAPK/ERK和PI3K/AKT信号通路在膀胱癌发生发展中具有重要作用，并且提示转录因子KLF5是这两条信号通路的潜在交汇点/枢纽。我们前期研究已证实KLF5在膀胱癌细胞生长、血管生成、迁移运动等方面发挥重要作用，同时预试验结果提示FGFR3表达受KLF5反馈调节。因此，我们推测膀胱癌中很可能存在FGFR3-KLF5正反馈调节环路，并且是驱动膀胱癌发生发展的关键机制之一。本项目拟综合应用shRNA慢病毒、表达谱测序、荧光素酶报告基因、ChIP、生物信息分析、免疫缺陷小鼠皮下成瘤等技术在体内和体外层面开展实验，以期：①揭示膀胱癌中FGFR3-KLF5正反馈环路之相互调节具体分子机制；②进一步理解膀胱癌发生发展复杂信号网络；③探索与之相关的膀胱癌分子诊断标记和靶向治疗策略。

For lacking of innovation in diagnosis and treatment, survival of bladder cancer patients has achieved no significant prolongation for decades. Recently, a number of studies have uncovered crucial roles of FGFR3 and its downstream MAPK/ERK and PI3K/AKT signaling pathways in the pathogenesis of bladder cancer, and also suggested that transcriptional factor KLF5 might serve as intersection / hub of the network. Our previous studies have confirmed important roles of KLF5 in cell proliferation, angiogenesis, and migration of bladder cancer. Interestingly, preliminary results point out FGFR3 itself is likely to be regulated directly by KLF5. Therefore, we speculate existence of FGFR3-KLF5 positive feedback loop in bladder cancer, which may be a key mechanism during bladder cancer development. By application of shRNA lentivirus, cDNA microarray, dual luciferase activity assay, ChIP, bioinformatics and xenografts in immunodeficiency mice, the project intends to： ① study roles and mechanisms of FGFR3-KLF5 positive feedback loop in bladder cancer；② further understand complicated molecular mechanisms of bladder cancer；③ provide reference frame for exploring new bladder cancer molecular diagnosis and targeted therapy strategies.