骨肉瘤恶性程度高、对放化疗不敏感，尚无靶向药物。我们用骨肉瘤细胞系进行了转录组测序、分析，发现并鉴定了一个新的融合基因（PABPC1-PCBD2，本项目称Fusion基因），在临床骨肉瘤标本中可用qRT-PCR、FISH、IHC检测。预实验表明：该Fusion基因可能是骨肉瘤的驱动基因之一，可增强细胞的迁移、侵袭和转移，其作用机制可能是活化NF-kB通路，该Fusion蛋白可分泌到exosome，并促进与其共培养的肿瘤细胞迁移、侵袭。本项目拟：进一步明确含有该Fusion蛋白的exosome可促进细胞的迁移、侵袭和转移作用；鉴定该Fusion蛋白形成exosome的机制；探讨该Fusion蛋白在骨肉瘤中的潜在治疗价值、临床意义；探讨用CRISPR-Cas9技术在小鼠中产生该Fusion基因，观察该小鼠是否发生骨肉瘤。本项目的完成，将为骨肉瘤的综合治疗、个体化疗法提供新靶标和新思路。

Osteosarcoma, a high malignant tumor, is insensitive to the current radio- and chemo-therapies, and there is no targeting drug available for this cancer so far. Using osteosarcoma cell lines, we have recently performed the mRNA sequencing analyses and identified and validated one of fusion genes, named as PABPC1-PCBD2 that is called the Fusion gene in this proposal, was detectable by qRT-PCR, FISH and IHC in clinical osteosarcoma samples. Our preliminary results showed that this Fusion gene is probably a driver for osteosarcoma, and obviously enhances the cell migration, invasion and metastasis probably through activating the NF-kB pathway, and that this Fusion protein is a secreted protein, which presents in exosome, and promotes migration and invasion of cells co-cultured with this exosome. This proposal plans to investigate the following events: To further confirm that the exosome containing this Fusion protein enhances the cell migration, invasion and metastasis; To identify the molecular mechanisms of this Fusion protein forming exosome; To explore the clinical potential of this Fusion gene/protein in the aspects of treatments and prognosis for the patients with osteosarcoma; Try to generate this Fusion gene and subsequently produce osteosarcoma in mice using the CRISPR-Cas9 technology. We believe that this proposal will provide a novel target for osteosarcoma and a new strategy for the treatments and individual therapies of osteosarcoma.