骨肉瘤中一个新Fusion蛋白的作用、机制和临床意义

项目名称： 骨肉瘤中一个新Fusion蛋白的作用、机制和临床意义

项目编号： No.81502512

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 廖丹

作者单位： 中山大学

项目金额： 16万元

中文摘要： 骨肉瘤恶性程度高、对放化疗均不敏感，尚无靶向药物。因此，寻找骨肉瘤特异性的治疗靶标，是其治疗的根本性问题和关键所在。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9个融合基因，其中一个融合基因是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：敲除或过表达该Fusion基因，可显著抑制或增强细胞的迁移、侵袭和转移，其作用机制可能是通过活化NF-κB信号通路从而促进细胞的迁移、侵袭。本项目拟：进一步明确该Fusion蛋白促进细胞的迁移、侵袭和转移的作用是通过激活NF-kB通路，并研究其活化的分子机制；临床样本中的p65核定位与该Fusion基因是否存在相关性；探讨该Fusion基因/蛋白是否在骨肉瘤中特异性存在。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。

中文关键词： 转移；融合基因；NF-KB；骨肉瘤

英文摘要： 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. Therefore, identifying the special therapeutic target(s) is crucial in the therapies of osteosarcoma. To reach this goal, using the osteosarcoma cell lines, we performed the mRNA sequencing analyses and identified and validated 9 fusion genes, 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 knockdown or overexpression of this Fusion gene obviously suppresses or enhances the cell migration, invasion and metastasis probably through activating the NF-kB pathway,. This proposal plans to investigate the following events: To further confirm that this Fusion protein enhances the cell migration, invasion and metastasis by activating the NF-kB pathway; To test whether the nulear p65 is related to the fusion protein in clinical samples; To explore whether the Fusion gene/protein specially exist in osteosarcoma. We believe that this proposal will provide a novel target for osteosarcoma and a new strategy for the treatments and individual therapies of osteosarcoma.

英文关键词： metastasis;fusion gene;NF-KB;osteosarcoma