APLN介导外泌体microRNA-195调控血管生成在肺癌侵袭和转移中的机制研究

云南宣威地区肺癌的发病率和死亡率位列全球首位，复发和转移是患者死亡的主要原因。血管生成是肿瘤转移的前提，microRNA对该过程有关键调控作用，外泌体作为microRNA的载体，在液体活检领域有显著优势。大样本分析揭示，miR-195 在宣威肺癌中表达降低，APLN是其靶基因，后者编码的Apelin蛋白与受体APJ结合形成Apelin /APJ系统，Wnt/β-catenin通路在该系统与外泌体调控血管生成中扮演了重要角色。本研究拟通过临床分析、细胞实验、动物模型等手段，研究miR-195 与 Apelin /APJ系统的相关性和临床意义，探讨对肺癌血管生成及转移的影响及作用机制，从分子、细胞及器官水平揭示存在“外泌体miR-195→Apelin/APJ系统→Wnt/β-catenin→血管生成→侵袭转移”的分子事件，为研发云南区域性高发肺癌转移预警标志和潜在的干预靶点提供依据。

The incidence and mortality of Yunnan Xuanwei lung cancer ranks first in the world. Recurrence and metastasis are the main causes of death in patients. Angiogenesis is a prerequisite for tumor metastasis, and microRNA has a key role in the process. As a carrier of microRNA, the exosomes has significant advantages in the field of liquid biopsy. The large sample microarray analysis revealed miR-195 is specifically reduced in Xuanwei female lung cancer patients and APLN was a key target gene of it. The APLN encodes Apelin, which combines with APJ to form Apelin /APJ system. The Wnt/β-catenin pathway plays an important role in the regulation of angiogenesis by the Apelin /APJ system and the exosomes. The study will research the correlation between exosomes miR-195 and Apelin /APJ system to explore the clinical significance. We also want to explore their influence on angiogenesis, metastasis of lung cancer and the mechanism from molecular, cell and organ level through the clinical analysis, cell function assay and animal model method. All above work is to revealed the existence of events "exosomes miR-195→Apelin/APJ system→Wnt/beta-catenin→tumor angiogenesis→invasion and metastasis of lung cancer”, which will provide important experimental evidence for developing early metastasis diagnostic biomarker and potential intervention or therapy target in Yunnan lung cancer with high incidence .