如何早诊、继而早治是提高胶质瘤生存率的关键问题。我们前期研究发现早期无症状胶质瘤大多具有异柠檬酸脱氢酶1(IDH1)突变,并且IDH1突变胶质瘤具有岛叶位置偏好性,开展相关分子机制研究将有助于发现新的胶质瘤分子靶标。基于预实验证据，我们推测其位置偏好性可能和神经干/前体细胞（NSC/NPC）IDH1突变后迁移能力减弱有关, 而IDH1突变NSC/NPC的外泌体中miR-377升高,继而调控其下游PAK1/ LIMK1通路可能为其作用机制。本项目拟在细胞和动物模型上,借助多种技术手段系统研究揭示NSC/NPC细胞中引入IDH1突变后,外泌体来源miR-377/ PAK1/ LIMK1通路变化以及对细胞迁移和位置分布的影响和分子机制，并通过临床标本验证miR-377诊断价值。本研究的成功实施将有助于发现IDH1突变胶质瘤的起源相关分子机制和建立胶质瘤的无创早期诊断。

Early diagnosis and early treatment is the key to improve the survival of glioma . We found that early asymptomatic gliomas mostly harbor isocitrate dehydrogenase 1 (IDH1) mutation. Our early studies revealed that IDH1 mutant glioma prefer to the insular location, the exploration of IDH1 mutant glioma location-preference is helpful to discover early cancer markers, we hypothesized that cell migration is attenuated in IDH1 mutated neural stem cells (NSC) /neural progenitor cells (NPC) which might result from downregulation of PAK1/ LIMK1 by the exsomal miR-377. In the present study, we will introduce the IDH1 R132H into NSC/ NPC to explore the effect of IDH1 mutation on migration and distribution of NSC/ NPC along with the changes of exsomal miR-377 / PAK1 /LIMK1 signaling pathway. These hypotheses will be also investigated in fetal rat modle. Finally, its diagnostic value will be verified by clinical analysis. Our study will focus on the underlying mechanism of IDH1 mutant glioma location preference and confirm the cell origin of IDH1 mutant glioma, it will lay a good foundation for the study on the oncogenesis of IDH1 mutated glioma and help non-invasive early diagnosis for glioma.