长链非编码RNA BGL3的互作蛋白Ku70在Abl诱导细胞癌变中的作用

项目名称： 长链非编码RNA BGL3的互作蛋白Ku70在Abl诱导细胞癌变中的作用

项目编号： No.81502397

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： 郭桂杰

作者单位： 中国科学院微生物研究所

项目金额： 20万元

中文摘要： 长链非编码RNA（lncRNA）的异常表达与肿瘤发生发展密切相关。我们在前期研究中发现lncRNA-BGL3在Abl癌基因诱导细胞转化过程中发挥重要作用，并鉴定到其互作蛋白Ku70。Ku70在DNA双链断裂的非同源末端连接修复途径中起关键作用，但是Ku70在Abl诱导细胞癌变中的作用仍不清楚。因此，本项目将进一步验证lncRNA-BGL3与Ku70在Bcr-Abl阳性癌细胞中的互作关系；进而应用敲低/高表达Ku70的Abl转化细胞模型，Ku70敲低转基因小鼠模型，结合表达谱芯片和蛋白质谱分析，在分子、细胞及动物水平上系统研究Ku70在Abl诱导细胞转化过程中的作用及其机理；最后，我们将应用特定细胞系和lncRNA-BGL3转基因小鼠探讨lncRNA-BGL3与Ku70互作对Abl阳性肿瘤发生发展的影响。本研究不仅能加深对Abl诱导细胞癌变机制的认识，对Abl阳性白血病的治疗也有指导意义。

中文关键词： C25_其它肿瘤；Abl癌基因；长链非编码RNA；细胞转化

英文摘要： Aberrant expression of long noncoding RNAs (lncRNAs) is associated with various human cancers. In previous study, we found that lncRNA-BGL3 critically regulated cellular transformation induced by Abl oncogenes, and identified the lncRNA-BGL3 interacting protein Ku70. Ku70 has been shown to play important roles in double strand break (DSB) repair by non-homologous end joining (NHEJ). However, the function of Ku70 in Abl-mediated cellular transformation is still unknown. In this project, we will further confirm the interaction between lncRNA-BGL3 and Ku70 in Bcr-Abl-positive cells. Moreover, we will use a set of in vitro and in vivo models including Ku70 knockdown/overexpressing Abl-positive cell lines and Ku70 knockdown transgenic mice, in combination with gene expression profile array and proteome analysis, to reveal the role and its mechanism for Ku70 during Abl-mediated tumorigenesis. In addition, we will investigate how the interaction between lncRNA-BGL3 and Ku70 affects Abl-induced tumorigenesis using specific cell lines and lncRNA-BGL3 transgenic mice. These studies may provide novel insights into complex mechanisms underlying Abl-mediated transformation, and be of significance to the treatment of Abl-induced hematopoietic malignancies.

英文关键词： other tumors;Abl oncogene;long noncoding RNA;cellular transformation