MSI2基因在胶质瘤中的功能和作用机制研究

Glioma is the most common tumor of central nervous system. The overall prognosis remains poor under current therapy. Thus, it is of great value to further explore the mechanisms of tumorigenesis and new therapies of glioma.Our previous work revealed that MSI2, a stem cell related gene, was overexpressed in glioma, and exhibited even higher expression in higher grade glioma and tumorsphere. Depletion of MSI2 resulted in decreased cell proliferation ability and impaired invasion potential, demonstrating that MSI2 may be closely associated with gliomagenesis. In this project, we will further confirm MSI2 overexpression in glioma, and analyze the correlation between MSI2 overexpression and glioma prognosis. MSI2 activation mechanisms in glioma will be examined from perspectives of gene mutation, DNA amplification and transcription factor regulation. The function of MSI2 in glioma will be explored through cell transformation, animal model, and stemness study. The mechanisms of MSI2 action will be investigated by using MudPIT, gene transfection, RNAi, microarray and proteomic methods. Successful execution of this project will be greatly beneficial for us to understand the mechanisms of gliomagenensis and to identify novel prognostic marker and/or therapy target for glioma.

胶质瘤是最常见的原发性中枢神经系统肿瘤，目前其总体疗效欠佳，深入探讨其发病机制并寻找有效治疗方法具有重要意义。前期工作中，我们发现干细胞相关基因MSI2在胶质瘤中高表达，在胶质母细胞瘤和肿瘤球中表达更高，而其表达下调可导致胶质瘤细胞的增殖、侵袭能力的下降，说明MSI2可能与胶质瘤发生发展密切相关。本研究拟进一步探讨MSI2在胶质瘤中的表达及其与胶质瘤预后的关系；从基因突变、基因扩增、转录因子调控等方面探讨MSI2的活化机制；用细胞转化、动物模型、干性研究等方法探讨MSI2的功能；用MudPIT、转基因、RNAi、microarray、蛋白质组学等方法深入探讨MSI2的作用机制。本研究对阐明胶质瘤的发病机理及寻找可用于治疗和预后的新靶标具有重要意义。

胶质瘤是最常见的原发性中枢神经系统肿瘤，深入探讨其发病机制并寻找有效治疗方法具有重要意义。前期工作中，我们发现干细胞相关基因 MSI2在胶质瘤中高表达，在胶质母细胞瘤和肿瘤球中表达更高，而其表达下调可导致胶质瘤细胞的增殖、侵袭能力下降，提示 MSI2 可能与胶质瘤发生发展密切相关。实施本项目，明确了MSI2与胶质瘤发生、发展、复发、耐药、预后和干性的相关性；研究了MSI2在胶质瘤中活化的机制；明确了MSI2在胶质瘤的功能和作用分子机制；筛选了胶质瘤中MSI2相互作用蛋白。本研究对阐明胶质瘤的发病机理具有重要意义，为发展以MSI2为靶标的胶质瘤治疗新策略提供了重要线索。