TREX1对骨肉瘤侵袭转移的影响及相关分子机制研究

Recent studies have found that TREX1 gene mutation was closely related to human four kinds of autoimmune diseases, but the relationship of the TREX1 and tumorigenesis and metastasis is unclear. Based on our initial study of the expression of TREX1 between on CD133+ osteosarcoma cells and of CD133- osteosarcoma cells exist significant differences, this project using RNA interference, gene transfection, Confocal Laser Scanning Microscopy and immune total precipitation (IP) method combined with osteosarcoma nude mouse model in vivo experiments to further investigate the subcellular localization, radiotherapy, chemotherapy, drug sensitivity, of TREX1 in the CD133+ osteosarcoma stem cells, to classify the effect of TREX1 on osteosarcoma growth, invasion and metastasis, and tumor immune escape. This study will help us to further understand the immune function of the new molecular and its roles in the recurrence, metastasis and pathological mechanism of osteosarcoma, and provide the experimental basis for using TREX1 as a new molecular target for the treatment of osteosarcoma.

新近研究发现TREX1基因突变与人类四种自身免疫性疾病密切相关，但是关于TREX1与肿瘤发生和转移的关系尚不清楚。基于对TREX1在CD133+骨肉瘤干细胞和CD133-骨肉瘤细胞中表达存在明显差异的初步研究基础上，本项目综合运用RNA干扰、基因转染、共聚焦激光扫描显微镜技术与免疫共沉淀（IP）方法并结合骨肉瘤裸鼠模型体内实验，进一步深入研究TREX1在CD133+骨肉瘤干细胞的亚细胞定位、对放疗、化疗药物敏感性的影响，明确TREX1在骨肉瘤的生长、侵袭和转移，及肿瘤免疫逃逸中的作用。从而进一步认识免疫新分子的功能及其在骨肉瘤复发和转移病理机制中的作用，为将TREX1作为骨肉瘤治疗新的分子靶点提供实验依据。

新近研究发现TREX1基因突变与人类四种自身免疫性疾病密切相关，但是关于TREX1与肿瘤发生和转移的关系尚不清楚。我们实验结果发现在不同人骨肉瘤细胞中，TREX1在CD133+骨肉瘤干细胞中表达明显低于CD133－骨肉瘤细胞。运用RNA干扰技术减少TREX1在CD133－ HOS骨肉瘤细胞中的表达，降低了对化疗药物敏感性；而应用基因转染方法增加TREX1在CD133+ HOS骨肉瘤干细胞中的表达，不仅增强了对化疗药物敏感性，而且促进了骨肉瘤的生长、侵袭和转移。本项目通过深入研究TREX1在CD133+骨肉瘤干细胞对化疗药物敏感性的影响，初步探明了TREX1在骨肉瘤的生长、侵袭和转移中的作用。从而进一步认识免疫新分子的功能及其在骨肉瘤复发和转移病理机制中的作用，为将TREX1作为骨肉瘤治疗新的分子靶点提供实验依据。