COPS3在骨肉瘤细胞干细胞样转化中的作用机制研究

项目名称： COPS3在骨肉瘤细胞干细胞样转化中的作用机制研究

项目编号： No.31470075

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 陈军

作者单位： 中国人民解放军第四军医大学

项目金额： 30万元

中文摘要： 骨肉瘤干细胞通常来源于恶变的间质干细胞，此外在外界因素的诱导下，骨肉瘤细胞（非骨肉瘤干细胞组分）也可经上皮间质转化而成为骨肉瘤干细胞，其分子机制尚未阐明。我们在前一国科金研究中发现：COPS3在骨肉瘤干细胞中的表达水平显著高于非干性骨肉瘤细胞；上调COPS3的表达可促使骨肉瘤细胞干细胞样转化，而c-myc是COPS3过表达的潜在调控分子。由此我们推断在骨肉瘤细胞干细胞样转化过程中存在c-myc-COPS3调控机制。为了证实上述假设，本研究拟通过多种研究手段证实COPS3促进骨肉瘤细胞干细胞样转化的作用，探讨c-myc对COPS3的转录调控机制，明确c-myc-COPS3调控机制对骨肉瘤细胞干细胞样转化的意义。本研究将为寻找新的骨肉瘤治疗靶点、开发新的治疗策略提供理论依据。

中文关键词： COPS3；c-myc；干细胞样转化；；

英文摘要： Usually it is believed that osteosarcoma stem cells（stem like osteosarcoma cells） are derived from malignant mesenchymal stem cells, or transformed from osteosarcoma cells (not stem cell components) through EMT(epitheilal-mesenchymal transition) under the induction of some external factors. But the mechanism is not clarified, so far. Our study found that: 1. COPS3 expression level in osteosarcoma stem cells is significantly higher, 2. Up-regulation of COPS3 expression responsible for the acquisition of stemness in osteosarcoma cells. 3. c-myc is the potential regulation molecules of COPS3 overexpression; 4. PRDX1---COPS3 candidate interaction protein --- is close related to the stem cell-like transformation of tumor cells. Hence we infer that there is a "c-myc-COPS3-PRDX1 regulatory mechanism" in the process of stem cell-like transformation of osteosarcoma cells. To verify this hypothesis, this research intends to confirm the role of COPS3 in promoting the transformation of osteosarcoma cell to stem cell through a variety of methods; discuss the mechanism of the transcriptional regulatory role of c-myc in COPS3 transcription; define the interaction between COPS3 and PRDX1, and find the significance of this interaction in stem cell-like transformation of osteosarcoma cells; finally verify the correlation between

英文关键词： COPS3；c-myc；stem like transformation；；