非小细胞肺癌(NSCLC)危害严重，侵袭转移是影响预后的关键原因。外泌体是肿瘤微环境中影响肿瘤细胞侵袭转移的一个重要因素，我们前期研究证实NSCLC患者血清和肿瘤细胞株上清中外泌体数量显著高于正常对照，且与患者的临床分期和转移呈正相关关系；患者组织及细胞株miRNA测序发现部分miRNA分子与外泌体释放及患者的转移预后显著相关；进一步功能研究发现NSCLC细胞中低水平的miR-124极显著的提高了外泌体的分泌，过表达miR-124可显著降低外泌体的释放，抑制Rab27a的蛋白水平。本课题拟从miR-124调节Rab27a水平为切入点，研究miR-124调控外泌体分泌的中间过程并挖掘miR-124的上游调控分子，最终阐明NSCLC肿瘤细胞外泌体释放调控的关键分子机制。本课题不仅有助于拓展NSCLC侵袭转移调控的知识领域，并为开发新的肺癌转移治疗靶点和转移预后判断指标提供重要线索和新的视角。

Non-small cell lung cancer (NSCLC) is a serious malignant tumor with dismal prognosis. Invasion and metastasis are the leading reason for the resultant mortality of patients with NSCLC. Exosomes in tumor microenvironment is one of the most important factor to influence the invasion and metastasis of tumor cells. Our previous study confirmed that the number of exosomes in serum of NSCLC patients and supernatants of tumor cell was significantly higher than that of normal controls, and significantly positive relevant with clinical stage and metastasis in NSCLC patients. MiRNA sequencing for patient tissue and cell line revealed that some of the miRNA molecules were significantly associated with the release of exosomes and the prognosis of metastasis. Further study found that low levels of miR-124 in NSCLC cells significantly improved the secretion of exosomes; overexpression of miR-124 significantly reduced the release of exosomes and inhibited the expression of Rab27a protein obviously. This study intends to use the regulation of Rab27a by miR-124 as a breaking point, studying the intermediate process for the secretion of exosomes and the upstream regulatory molecules for miR-124, to clarify the molecular mechanisms of highly secretion of exosomes by NSCLC cells. This study will not only help further expand the knowledge field of invasion and metastasis regulation in NSCLC, and also may provide important clues and new perspective for the development of new target and prognosis indicators in NSCLC.