DNA修复基因XPC促进细胞凋亡、细胞周期阻滞或DNA修复等过程，有助于维持基因组稳定性。我们前期工作已首次证实膀胱癌发生、发展与XPC表达缺陷密切相关。基于后续研究初步发现热休克转录因子1（HSF1）在膀胱癌中高表达以及潜在“HSF1-miR449b-XPC”转录调控通路的重要线索，本研究将深入探讨膀胱癌XPC基因沉默机制。从分别证实“HSF1— miR449b” 、“mir449b—XPC”的关键转录调控作用入手，确立“HSF1-miR449b-XPC”级联调控通路；结合临床关联性研究，联合细胞学与动物学研究，采用外源基因干预策略，证实膀胱癌HSF1异常高表达通过上调miR-449b抑制XPC介导的DNA损伤应答，促进肿瘤发生、发展的作用与机制。本研究将揭示HSF1、Mir-449b在DNA损伤应答与肿瘤中的崭新角色，有助于阐明肿瘤高遗传不稳定性机制，有望为膀胱癌早期诊断提供新策略

The XPC protein play important roles in the DNA damage respone, including the process of cell cycle arrest, apoptosis, and DNA repair, which is critical for the maintenance of gemomic stability. We have firstly reported that the attenuated expression of XPC protein is associated with the carcinogenesis of bladder cancer. In the following unpublished data, the overexpression of the protein of heat shock factor (HSF1) is observed in bladder cancer and the “HSF1-miR449b-XPC” regulation pathway is potentially exsited in both HEK293 and bladder cancer cells. We aim to investigate the regulatory mechanism of XPC gene silencing in bladder cancer and the role of “HSF1-miR449b-XPC” pathway in this project. Firstly, we will make an effort to prove that miR449b being a direct target of transcriptional factor HSF1 and XPC being a direct target of miR449b. Secondly , we will explore the existance and importance of the “HSF1-miR-449b-XPC” pathway in bladder cancer. Combined the associated studies of clinical ,bladder cancer cells and animal models, with the strategies of gene interference (shRNA-HSF1, mir449 mimmics), we will try to prove the overexpression of HSF1 inhibit the XPC-mediated DNA damage response and is contributed to the carcinogenesis of bladder cancer , via promoting the expression of mir-449b. With our studies in the future, it is not only hopeful to expose the novel role of HSF, Mir449b in the DNA damage response and carcinogenesis, and also provide the new cancer diagonosis marker based on XPC defection.