CIRP 增强Wnt/β-catenin通路促进肺癌侵袭转移的分子机制研究

侵袭转移是肺癌治疗的难点之一。我们前期研究发现，肺腺癌细胞中显著高表达CIRP和β-catenin分子，它们高表达均与肺腺癌恶性程度以及淋巴结转移正相关，与患者总生存率负相关，并且CIRP异常定位于细胞质。沉默CIRP基因显著降低β-catenin表达，并减弱A549细胞的迁移和侵袭能力。实验还证实CIRP蛋白能够增强β-catenin mRNA的稳定性。基于以上发现我们认为：异常定位表达的CIRP调控Wnt/β-catenin信号通路在肺癌发展进程以及侵袭转移过程发挥了重要作用。本研究拟以肺癌细胞株及原代肺癌细胞为研究对象，在临床、细胞及动物水平研究CIRP的生物学功能以及其对Wnt/β-catenin通路的调控作用。课题研究将深入阐明CIRP促进肺癌发展及侵袭转的作用机制，是对目前肺癌发生发展机制理论的补充和深入，将为临床探索提供新的理论依据，为治疗提供新的作用靶点。

Invasion and metastasis is a key problem for lung cancer treatment. Our previous study found that: CIRP and β-catenin are highly expressed in lung adenocarcinoma cells. Their elevated expression is positively correlated with the malignancy of tumors and the ability to metastasize, while negatively related to the patients' overall survival. We also observed that CIRP abnormally located in cytoplasm. Silencing CIRP gene can significantly decrease β-catenin expression and reduce the migration and invasion ability in A549 cells. Moreover, our results verified that CIRP protein can bond with β-catenin’s mRNA and enhance its stability in cells. Based on these results, we propose that abnormally expressed and relocated CIRP plays an important role in invasion and metastasis process of lung cancer cells via regulating the Wnt/β-catenin signaling pathway. In this project, lung cancer cell lines and primary lung cancer cell will be used at clinical, cell and animal level to investigate the function of CIRP and its effect on Wnt/β-catenin signaling pathway. It will elucidate and further complement and deepen the mechanism of how CIRP promotes the development, invasion and metastasis of NSCLC. This project will provide new theoretical foundation for clinical exploration the occurrence and progression of NSCLC, and future findings may provide original intervention target for lung cancer treatment.