胶质母细胞瘤是最常见的颅内恶性肿瘤，往往伴有持续激活的STAT3。我们前期发现精氨酸甲基转移酶Prmt2敲低的小鼠胶质母细胞瘤细胞成瘤能力显著减弱；在人胶质母细胞瘤细胞中敲低PRMT2导致STAT3失活。此前一项研究发现PRMT2能够催化STAT3精氨酸甲基化，因此我们提出假说：PRMT2催化STAT3甲基化，通过交互作用促进其磷酸化，而参与胶质母细胞瘤发生发展。本项目拟进一步观察PRMT2敲低或者其酶活性缺失对人胶质母细胞瘤细胞增殖、凋亡、克隆形成能力和体内成瘤能力的影响，同时检测PRMT2与STAT3的相互作用，鉴定STAT3精氨酸甲基化位点，明确STAT3甲基化对其磷酸化和转录活性的作用、对其促瘤功能的影响；并结合临床标本分析PRMT2在不同类型不同级别胶质瘤中的表达情况，探讨其与STAT3磷酸化水平的相关性和患者预后、生存期之间的联系，为胶质母细胞瘤的治疗提供新的靶点和理论基础。

Glioblastoma is the most common and aggressive form of intracranial tumors. Constitutive STAT3 activation is usually found in glioblastoma. We previously found that one of the Protein Arginine Methyltransferases Prmt2 was essential for the in vivo tumorigenesis in the mouse model. Therefore we turned our attention to the effects on human glioblastoma and we noticed that PRMT2 depletion downregulates STAT3 phosphorylation. It was ever reported that PRMT2 directly targets STAT3 for arginine methylation. Therefore we wonder whether PRMT2 activates STAT3 signaling via STAT3 methylation and promotes tumorigenicity of glioblastoma cells. Here we propose a careful examination of the effects of downregulation of PRMT2 protein level and catalytic activity on human glioblastoma cell proliferation, apoptosis, tumorigenicity in vitro and in vivo. Meanwhile we will examine the protein-protein interaction between PRMT2 and STAT3. After figuring out the methylation site(s), we would like to see how the methylation affects STAT3 phosphorylation, its transcriptional activty and its tumorigenic functions. In addition, we will examine the expression levels in different types and grades of clincial gliomas and link it to the phosphorylation level of STAT3 and the patients prognosis. This study will hopefully identify a new target and provide a novel therapeutic strategy for future glioblastoma treatment.