LncRNA-G8在葡萄糖饥饿应激时调控肿瘤细胞DNA损伤修复的功能和机制研究

全球第二大致死因素癌症严重影响人类健康，而且其诊断治疗难度较大。肿瘤细胞的能量需求增加和基因组不稳定性是癌症的重要特征，而且肿瘤细胞DNA损伤修复依赖有氧糖酵解提供大量能量。长非编码RNA在癌症发生发展过程中发挥着重要作用，但是lncRNA在葡葡萄糖代谢调控肿瘤细胞DNA损伤修复的过程中发挥的功能及其中的分子机制还不清楚。本项目初步发现，响应葡萄糖饥饿应激的lncRNA-G8促进肿瘤细胞DNA损伤修复，而且HMGB1在其中发挥重要介导作用。后续我们拟从体外培养肿瘤细胞、小鼠动物模型和TCGA临床样本数据库多个层面入手，通过细胞生物学、生化分子生物学、生物信息学和实验动物学等多种的研究手段，研究lncRNA-G8响应葡萄糖饥饿应激并调控肿瘤细胞DNA损伤修复的信号通路，并阐明其生理病理意义。总之，本项目将为深入理解癌症的发生发展以及癌症的治疗提供理论基础。

Cancer, which is the second leading cause of death globally, seriously affects human health and is difficult to be diagnosed and treated. Increased energy requirements and genomic instability of tumor cells are important features of cancer. Moreover, tumor cells mainly rely on aerobic glycolysis to provide sufficient energy for DNA damage repair. Long noncoding RNA plays an important role in tumorigenesis. However, the function of lncRNA in tumor cells DNA damage repair regulated by glucose metabolism and associated molecular mechanism remain unclear. In this project, we find that lncRNA-G8, in response to glucose starvation, promotes DNA damage repair in tumor cells. Furtherly, HMGB1 mediates this progress. In this project, we plan to investigate the signaling pathways of lncRNA-G8 in regulation of tumor cells DNA damage repair under glucose starvation via virous methods (such as cell biology, biochemical and molecular biology, bioinformatics, and experimental zoology) in TCGA clinical sample database, in vitro cultured tumor cells and in vivo mice model. Furthermore, we will elucidate the physiological and pathological implications of this study. In sum, this project will provide theoretical basis for the in-depth understanding of the tumorigenesis and the treatment of cancer.