我们前期研究表明，肿瘤外泌体既介导CAFs代谢重编程又能诱导促血管生成表型，但二者之间是否存在共同的分子开关并不清楚。miRNAs具有广泛的基因调节功能，是介导肿瘤-基质细胞对话的重要信使。因此，本课题提出“外泌体miR-155/PGC-1α通过介导CAFs代谢重编程调控口腔鳞癌CAFs促血管生成表型”，重点探讨：①口腔鳞癌外泌体调控CAFs代谢重编程及促血管生成表型；②miR-155对调控CAFs代谢重编程的调控；③PPARγ/PGC-1α对CAFs代谢重编程及促血管生成表型的门控作用；④miR-155调控CAFs中PPARγ/PGC-1α和ROS的机制；⑤ROS/PFKFB3介导的代谢重编程在miR-155诱导CAFs促血管生成表型中的机制。本课题对阐明口腔鳞癌外泌体介导的代谢重编程调控CAFs促血管生成表型的全新分子机制，以及筛选针对CAFs的新型治疗靶标均具有重要意义。

Exosomes are important messengers of intercellular communication that mediate tumor-stromal cell interactions. Our previous studies confirmed that tumoral exosomes mediated metabolic reprogramming of cancer-associated fibroblasts (CAFs) and induced their pro-angiogenic phenotype via transferring miR-155, but the association between the metabolic reprogramming and pro-angiogenic phenotype acquisition of CAFs is unclear. In conjunction with other findings, we propose that "exosomal miR-155 regulates the pro-angiogenic phenotype of oral squamous cell carcinoma (OSCC)-CAFs by mediating their metabolic reprogramming". This project aimed mainly to investigate: ⅰ) roles of OSCC-exosome in the regulation of metabolic reprogramming and pro-angiogenic phenotype of CAFs;ⅱ) roles of exosome-mediated miR-155 transmission in the regulation of CAFs activation and metabolic reprogramming; ⅲ) gating effect of PPARγ/PGC-1α on metabolic reprogramming and pro-angiogenic phenotype acquisition of CAFs in OSCC; iv) mechanisms underlying the regulation of PPARγ/PGC-1α expression and ROS levels in CAFs by OSCC-exosomal miR-155; v) mechanisms underlying the regulation of miR-155-mediated pro-angiogenic phenotype acquisition by ROS/PFKFB3-mediated metabolic reprogramming. This study links exosome-mediated intercellular communication, miRNA-governed gene regulation, metabolic reprogramming, and pro-angiogenic phenotype of CAFs and explore the role of exosome-mediated metabolic reprogramming in regulating the pro-angiogenic phenotype acquisition of CAFs in OSCC.