众所周知，由PTRF/Cavin与Cavelin共同参与了细胞窖形成和细胞内吞过程；本课题组首次发现PTRF参与外泌体的形成以及细胞内生物分子的外向运输和细胞间的物质交换。本课题集中在“PTRF/Cavin参与胶质瘤外泌体形成机制与靶向治疗”。应用免疫沉淀技术细胞层次上分析RTK信号通路活性与PTRF启动子区域H3K4/H3K27修饰的调控关系、明确信号通路对PTRF基因的表达调控模式；进一步应用EGFRVIII稳转细胞模型免疫沉淀、萤光定位分析等方法研究PTRF基因是否参与了外泌体Cav-1/EGFRVIII的募集机制，应用基因编辑技术或者RNAi技术分析PTRF对外泌体生成的决定作用。应用纳米胶技术设计出肿瘤靶向性的PTRF基因修饰投递体系，利用裸鼠原位移植瘤模型研究PTRF对胶质瘤局部微环境重构的逆转效应。本研究可以明确胶质瘤外泌体表面的新标识物的致病机制，并具有临床转化潜在价值。

It is well known that PTRF / Cavin and Cavelin participate in the process of caveolae formation and cell endocytosis. Our group, for the first time, finds that PTRF is involved in the formation of exosomes, the outward transport of intracellular biomolecules and the exchange of substances between cells. This topic focuses on "PTRF / Cavin involved in glioma exosomes formation mechanism and targeted therapy." In order to clarify the control mode of signal pathway for PTRF expression, the relationship between RTK signal pathway activity and the regulation of H3K4 / H3K27 modification in PTRF promoter region will be analyzed by immunoprecipitation technique. Furthermore, we will investigate whether the PTRF gene is involved in the recruitment of Cav-1 / EGFRVIII in EGFRVIII stably transfected cell line model by fluorescence localization analysis and immunoprecipitation technology, and analyze the role of PTRF in the production of exosomes by gene editing technology or RNAi technique. To study the reversal effect of PTRF on local microenvironment reconstruction of glioma, we design a tumor targeting PTRF gene delivery system utilizing nanogel technique via orthotopic implanted tumor model in nude mice. This study can clarify the pathogenic mechanism of the new marker on the surface of exosomes in glioma, and provides the potential value of clinical transformation.