脂代谢重塑是胶质母细胞瘤（GBM）代谢改变的重要特征，与肿瘤恶性进展及放化疗抵抗密切相关。我们前期发现缺氧的GBM细胞脂代谢通路异常激活，但具体机制不明。已知癌基因ZEB2受缺氧关键因子HIF-1α的调控。生信分析及预实验表明，ZEB2与RBMX可能为相互作用蛋白，干扰ZEB2后GBM细胞脂滴堆积下降。且RBMX与SCAP第17号外显子有多个结合位点，SCAP第17号外显子跳跃的剪接模式抑制了GBM细胞脂质合成关键因子SREBP-1的激活，而此过程能够被缺氧所逆转。据此，本项目拟利用转基因技术、CoIP、ChIP、FRET、同位素脂质标记、体内外功能实验，证实在缺氧微环境下HIF-1α通过上调ZEB2的表达，促进RBMX对SCAP剪接模式的调控，激活SREBP-1介导的脂肪酸从头合成，导致GBM内脂滴的堆积。本项目将阐明GBM脂代谢重塑的一个关键分子机制，为控制GBM复发提供新的治疗靶点。

Lipid remodeling is an important feature of the metabolism alterations of glioblastoma (GBM), which is closely related to the malignant progress of tumor and resistance to radiotherapy and chemotherapy. We previously found upregulated lipid metabolism in hypoxic GBM cells, but the specific mechanism remains unknown. It is known that oncogene ZEB2 is upregulated by hypoxia key factor HIF-1α.Bioinformatics analysis and preliminary experiments showed that ZEB2 may interact with RBMX, and the lipid droplet accumulation in GBM cells will be decreased after ZEB2 knockdown. Moreover, RBMX has multiple binding sites with exon 17 of SCAP. Exon 17 skipping of SCAP inhibits the activation of SREBP-1, a key lipid synthesis factor in GBM cells, and this process can be reversed by hypoxia . Therefore, this project intends to use transgenic technology, CoIP, ChIP, FRET, isotope lipid labeling, in vitro and in vivo experiments to confirme that HIF-1α upregulates ZEB2 to regulate the splicing pattern of SCAP through interaction with RBMX, and then activate SREBP-1-mediated de novo fatty acid synthesis, leading to the accumulation of lipid droplets within the GBM. This project will elucidate a key molecular mechanism of GBM lipid metabolism remodeling, and provide new therapeutic targets for the control of GBM recurrence.