Musashi 2促进膀胱癌增殖及耐药的分子机制

前期研究中我们首次报道，癌基因Musashi-2（Msi2）可促进膀胱癌细胞的侵袭和迁移。进一步研究发现过表达Msi2能显著促进膀胱癌细胞的增殖，增强膀胱癌细胞对化疗药物的抵抗能力；此外，Msi2能激活Wnt/β-catenin及JAK2/STAT3信号通路，但其具体的分子机制尚不清楚。本项目将以过表达和抑制Msi2的膀胱癌细胞为模型，通过RNA结合蛋白免疫沉淀、免疫共沉淀及荧光素酶报告基因分析等方法，探讨Msi2激活Wnt/β-catenin及JAK2/STAT3信号通路的具体分子机制；并进一步结合临床样本，验证Msi2促进膀胱癌细胞增殖及耐药的功能，为膀胱癌的诊治提供新的分子靶标。

Previously, we demonstrated for the first time that oncogene Musashi-2 (Msi2) could induce bladder cancer cell migration and invasion. Furthermore, our preliminary data demonstrated that overexpression of Msi2 induces proliferation and chemo-resistence in bladder cancer cell lines. Moreover, Msi2 could activate the Wnt/β-catenin and JAK2/STAT3 signaling pathway. However, the exact mechanisms involving the process remains unkown. Therefore, in the present project, we aim to employ RNA binding protein immunoprecipitation (Rip-ChIP), co-immunoprecipitation (Co-IP) and luciferase reporter assays in both in vivo and in vitro systems, and use clinical samples to investigate the mechanism of how Msi2 activate Wnt/β-catenin and JAK2/STAT3 signaling pathway during the development and progression of bladder cancer, which may provide new biomarkers and targets for the diagnosis and treatment of bladder cancer.