CDC25A调控RPL11-MDM2-p53信号通路促进肝癌细胞增殖的分子机制研究

目前研究表明细胞分裂周期因子25（CDC25A）是细胞周期的重要调控因子，在多种恶性肿瘤中高表达，与患者不良预后密切相关，但其调控肝癌细胞增殖的分子机制尚未完全明确。前期我们通过串联亲和纯化质谱（TAP-MS）筛选发现RPL11等核糖体蛋白（RPs）可能是与CDC25A互作的蛋白；通过基因芯片技术发现CDC25A可能与p53信号通路相关。已知RPs-MDM2-p53 信号轴在肿瘤的发生发展中扮演重要角色，因此我们推测CDC25A可能通过结合RPL11蛋白，进而调控MDM2-p53信号通路参与肝癌细胞的增殖。本项目拟通过验证CDC25A与RPL11的结合关系，观察CDC25A对p53通路的影响，证实RPL11介导CDC25A对MDM2-p53信号轴的调控作用，探讨CDC25A调控p53蛋白的机制，深入阐明肝癌发生发展的分子机理，期望为肝癌患者的诊疗提供新方向。

Current studies have shown that cell division cycle 25（CDC25A）is an important regulator of cell cycle, which is highly expressed in a variety of malignant tumors and closely related to the poor prognosis of patients，but its molecular mechanism for regulating the proliferation of hepatoma carcinoma cells has not been fully clarified. Through TAP-MS screening, we found that ribosomal proteins (RPs) such as RPL11 may be the proteins interacting with CDC25A. It was found that CDC25A might be related to p53 signal pathway by Affymetrix microarray. It is known that the RPs-MDM2-p53 axis plays an important role in the occurrence and development of tumor. Therefore, we speculate that CDC25A may regulate the MDM2-p53 signaling pathway to participate in the proliferation of hepatoma carcinoma cells by binding to ribosome proteins such as RPL11. In this study, “CDC25A could competitively bind to RPL11”, “The effect of CDC25A on p53 pathway.” and “The regulation of CDC25A on MDM2-p53 axis depends on RPL11.” three parts would be verified to investigate how CDC25A regulates p53 protein and elucidate the molecular mechanism of the development and progression of liver cancer, which provide a new direction for the diagnosis and treatment of liver cancer.