MED13介导的TRIP4/hTERT信号通路在维持肺癌干细胞干性中的作用及机制研究

肺癌干细胞是导致肺癌治疗失败及远处转移的重要原因，其干性的维持机制仍未完全清楚。中介复合体系统参与调控干细胞信号传导，其构成亚基MED13参与肿瘤的发展。申请人发现，敲低肺癌中MED13表达能抑制肺癌细胞的干性等能力，通过前期实验发现其与干性相关蛋白hTERT的表达存在正相关，并使调控蛋白TRIP4的泛素化减少。在此前期基础上，申请人假设MED13通过激活TRIP4/hTERT信号通路调节肺癌干细胞的干性。本课题将通过细胞实验、动物模型实验阐明MED13对肺癌干细胞干性维持的促进作用，利用免疫共沉淀、siRNA文库筛选等技术检测MED13维持肺癌干细胞干性的分子机制，并在临床标本中分析MED13与肺癌患者预后的关系，预期阐明MED13作为肺癌治疗靶点的可能性，在提供肺癌干细胞研究新思路的同时，探索非小细胞肺癌临床治疗的新方向。

Lung cancer stem cells are important causes of treatment failure and metastasis of lung cancer. The mechanism of stem cell traits is complicated. The mediator complex system is an important component in regulating cancer stem cell signaling, and its subunit MED13 is involved in tumor development. The applicant's previous research found that the expression of MED13 was increased in lung cancer cells and tissues, and it was related to the stem cell traits of the lung cancer cells. Further study found that MED13 interact with hTERT, and increased the stability of TRIP4 protein. Therefore, we hypothesized that MED13 could regulate the stem cell traits of lung cancer cells by activating the TRIP4/hTERT signaling pathway. This project intends to further use cell models and animal models to clarify the cell biology and animal in vivo functions of the MED13-TRIP4/hTERT signal in the maintenance of lung cancer stem cell traits, and to clarify the molecular mechanism of MED13 in maintaining the lung cancer stem cell traits. We plan to apply Co-IP and siRNA library screening technology to detect MED13 maintain the molecular mechanism of lung cancer stem cells. At last, we use clinical specimens to analyze the relationship between MED13 and the prognosis of patients with lung cancer, and provide a scientific basis for clarifying the clinical significance of MED13 as a therapeutic target.