目前肿瘤研究正在从单独关注肿瘤自身的信号调控逐渐拓展到肿瘤与周围微环境的信息交互。我们前期实验发现：缺氧微环境中胶质瘤干细胞通过分泌外泌体增强胶质瘤细胞耐药性和干性表型；胶质瘤干细胞中miR-30b-3p可被HIF1α上调，后经hnRNPA2B1分拣作用至外泌体。因此，我们提出“缺氧微环境下胶质瘤干细胞源性外泌体选择性运载miR-30b-3p调控胶质瘤细胞化疗耐药和干性表型”科学假说。课题拟探究缺氧微环境下胶质瘤干细胞中HIF1α对miR-30b-3p的转录调控和hnRNPA2B1介导的分拣作用，明确外泌体包裹的miR-30b-3p调节胶质瘤细胞化疗耐药和干性表型的机制，分析胶质瘤患者循环外泌体中miR-30b-3p的临床意义。课题将揭示缺氧微环境中胶质瘤干细胞源性外泌体调控胶质瘤细胞替莫唑胺耐药和干性表型的机理，为研究胶质瘤化疗耐药和发生发展提供新的思路。

Tumor research is gradually expanding from the signal regulation of the tumor itself to the interaction between the tumor and the surrounding microenvironment. Our previous studies found that in the hypoxic microenvironment, glioma stem cells played an important role in maintaining the self-renewal and chemoresistance of glioma cells via releasing exosomes. And HIF1α up-regulated the expression level of miR-30b-3p in glioma stem cells, which was then secreted to exosomes by hnRNPA2B1 sorting. Therefore, we proposed the hypothesis that exosomes derived from hypoxic glioma stem cells selectively transport miR-30b-3p to regulate chemoresistance and neurosphere formation ability of glioma cells. In this study, we tend to investigate the transcriptional regulation of HIF1α on miR-30b-3p and the sorting effect mediated by hnRNPA2B1, validate the potential mechanism of exosomal miR-30b-3p regulating chemoresistance and neurosphere formation of glioma cells, and analyze the clinical application of circulating exosomal miR-30b-3p in the diagnosis and treatment for glioma patients. In summary, our results will reveal the mechanism of exosomes, which are derived from hypoxic glioma stem cells, regulating temozolomide resistance and neurosphere formation of glioma. And it will provide a new idea for studying drug resistance and development of glioma.