端粒酶与肿瘤发生发展密切相关，研究其调控机制意义重大。我们前期用在酵母中建立的活体成像系统，发现TPR介导端粒酶的RNA组分TERC出核。数据库资料分析显示，TPR在肺癌组织中高表达，且与患者的不良预后相关。我们的进一步实验表明：TPR促进肺癌细胞生长和迁移；敲低TPR阻滞TERC出核，抑制TERC在细胞质介导端粒酶组装，进而下调细胞核内的端粒酶活性。据此，我们推测TPR在肺癌细胞中协调TERC出核及端粒酶成熟，从而增强端粒酶功能以促进肺癌发生发展。本项目拟在肺癌细胞和动物模型中，深入研究TPR对TERC出核与端粒酶功能的调控，明确其对细胞生长、凋亡、迁移和侵袭的作用。我们还将在组织标本中分析TPR的表达，以及TERC和端粒酶的定位与肺癌发生、分期、预后等的相关性，确定其临床意义。本项目旨在拓展对肺癌发病机制的认识，为确立TPR/TERC/端粒酶作为肺癌诊断标记和治疗靶点提供理论和实验依据

Telomerase is closely related to tumorigenesis and development. Therefore, it is of great significance to investigate its regulation mechanism. Using a live cell imaging system established in yeast, we have discovered that TPR mediates the nuclear export of the telomerase RNA component TERC. Database analysis has showed that TPR is highly expressed in lung cancer tissues, and is associated with poor prognosis in patients. Our further experiments have revealed that TPR promotes the growth and migration of lung cancer cells; knockdown of TPR blocks TERC nuclear export, inhibiting cytoplasmic TERC-mediated telomerase assembly, and thus leading to the down-regulated telomerase activity in the nucleus. Based on these results, we hypothesize that TPR coordinates TERC nuclear export and telomerase maturation in lung cancer cells, thereby enhancing telomerase functions to promote the development of lung cancer. In this project, we will elucidate the molecular mechanism by which TPR regulates TERC nuclear export and telomerase functions in lung cancer cells and animal models, and clarify its effects on cell growth, apoptosis, migration and invasion. Moreover, we will examine the expression of TPR, as well as the localization of TERC and telomerase in tissue samples, analyze their correlation with lung cancer occurrence, stage, prognosis, etc., and determine their clinical significance. This project aims to expand the understanding of the pathogenesis of lung cancer, and to provide both theoretical and experimental basis for establishing TPR/TERC/telomerase as a diagnostic marker and therapeutic target for lung cancer.