miR-550a-3-5p/YAP信号轴介导口腔鳞癌脂肪酸氧化重编程调控淋巴结转移的分子机制

淋巴结转移是口腔鳞癌（OSCC）预后评判最重要的指标；脂肪酸氧化（FAO）与肿瘤转移关系是肿瘤代谢领域的研究热点。最新研究显示，YAP诱导的肿瘤FAO可能在淋巴转移中发挥关键作用。鉴于此，在前期研究基础上提出科学假设：miR-550a-3-5p/YAP信号轴介导口腔鳞癌FAO重编程在调控淋巴结转移中发挥重要作用。围绕此假设，拟探讨：1.miR-550a-3-5p/YAP能否介导OSCC脂肪酸氧化从而调控淋巴结转移？2.miR-550a-3-5p/YAP在原发灶和淋巴转移灶中调控FAO是否具有可塑性？两者能否协同促进OSCC淋巴结转移？3.miR-550a-3-5p对YAP负性调控缺失后，YAP调控下游哪些关键转录因子、关键酶和分子促进FAO？研究结果将从肿瘤固有特征和微环境介导YAP调控脂肪酸氧化可塑性的新视角，从原发-转移灶全链条阐释口腔鳞癌淋巴结转移的分子机制，为临床防治提供新靶标。

Lymph node metastasis is the most important prognostic indicator of oral squamous cell carcinoma (OSCC). Currently, the relationship between fatty acid oxidation (FAO) and tumor invasion and metastasis is a hotspot in the field of tumor metabolism. Recent studies have shown that YAP-induced tumor plasticity in FAO metabolism may play a key role in lymph node metastasis. Based on our previous data, we propose a hypothesis that miR-550a-3-5p/YAP signal axis plays an important role in regulating lymph node metastasis by mediating FAO reprogramming of OSCC. The aim of this project is to investigate whether miR-550a-3-5p/YAP can mediate FAO of OSCC and play a key role in lymph node metastasis of OSCC, whether miR-550a-3-5p/YAP regulates the metabolic plasticity of FAO in primary tumor and metastatic lymph nodes of OSCC, as well as whether this metabolic plasticity of FAO can synergistically promote lymph node metastasis in OSCC. Furthermore, we also investigate the down-stream critical transcription factors, enzymes and signaling pathways of YAP signaling pathway promoting FAO during the deficiency of miR-550a-3-5p negative regulation. The results of this study will elucidate the molecular mechanism of lymph node metastasis in OSCC from the perspective of the intrinsic characteristics of tumor and the regulation of fatty acid oxidation plasticity by microenvironment mediated YAP, and provide a new target for clinical prevention and treatment of OSCC.