骨肉瘤（OS）肺转移发生早、死亡率高。最新发现外泌体在转移前微环境调控中发挥重要作用。我们前期证实OS外泌体被肺成纤维细胞摄取并促进肺转移；高通量测序并验证发现外泌体lncRNA ENST00000506942.1表达显著上调；敲低该分子，外泌体中表达也下调；以敲低及对照组外泌体预处理动物，经尾静脉接种OS细胞，敲低组肺转移结节较少。目前OS外泌体ENST00000506942.1在肺转移前微环境中的作用及机制尚未阐明。现拟在前期基础上运用细胞、动物模型验证OS外泌体ENST00000506942.1在肺转移前微环境中作用；应用生物信息分析、RNA pulldown等鉴定lncRNA-miRNA-mRNA调控机制；结合病例资料，分析外泌体ENST00000506942.1临床意义。本项目旨在研究OS源外泌体ENST00000506942.1在肺转移前微环境中作用及机制，探索OS肺转移新靶标

Osteosarcoma has a propensity to metastasize to the lung at early stage and with a high mortality rate. Recent studies suggested that exosoms played a critical role in the regulation pre-metastatic inche. Our previous research identified that the specific uptake of the osteosarcoma cell-derived exosomes occured in lung fibroblast cells and facilitated lung metastasis. Through sequencing and verification lncRNA ENST00000506942.1 was identified significant upregulated in exosomes. Furthermore knockdown this lncRNA in osteosarcoma cell influenced the downregulation of its level in exosomes. These exosomes were injected via tail vein, then low metastatic cell line ZOS were injected into these mice, and the number of lung metastatic node in the experiment group was substantially less than control group. Currently, the mechanisms and the role that are involved in the OS cell-derived exosome ENST00000506942.1 in lung pre-metastasis microenvironment have not yet been elucidated. Here,according to the previous studies, we plan to use osteosarcoma cell lines and animal models to verify the role of OS cell-derived exosome ENST00000506942.1 in lung pre-metastasis microenvironment; then identify the regulation network of ENST00000506942.1-micRNA-mRNA by means of RNA pulldown etc.; furthermore, according to clinical data, clinical significance of ENST00000506942.1 in exosomes would be analyzed. We aim to study the mechanisms and the role of OS cell-derived exosome ENST00000506942.1 in lung pre-metastasis microenvironment, with the purpose to shed light on the new therapeutic targets in lung metastasis.