Warburg效应被发现并研究超过了90年，而近十年更是癌症生物学最热门的研究方向之一。然而，神经肿瘤的代谢重编程还是一个相对未知的领域，尤其是Warburg效应在胶质母细胞瘤中的调控机制仍不甚清楚。许多研究表明转录因子在肿瘤的代谢重编程中起关键作用。我们的前期研究发现转录因子YY2在胶质母细胞瘤中表达异常升高，与肿瘤恶性程度和致死高度相关，是其中风险比值最高的转录因子之一。GRO-seq全基因组新生RNA测序鉴定发现YY2作为关键转录因子促进葡萄糖酵解途径中所有重要酶基因转录激活。过量表达YY2会促进糖酵解酶基因表达和细胞外酸化，其缺失导致癌细胞糖酵解耗氧量的显著下降。由此，本项目将集中研究YY2作为胶质母细胞瘤中调控Warburg效应的关键转录因子，驱动糖酵解酶基因转录，支持脑胶质瘤营养摄取和代谢重编程途径的功能和分子机制，并探讨以YY2活性作为新型脑胶质瘤药物靶点开发的可能性。

Despite that the Warburg effect has been discovered and studied for more than 90 years, it remains as one of the most attractive areas in cancer biology. However, metabolic reprogramming in brain tumors still remains poorly understood, especially the molecular mechanisms governing the Warburg effect in glioblastoma (GBM). It is well known that transcription factors play a vital role in the regulation of metabolic reprogramming. Our preliminary data revealed that transcription factor YY2 is highly expressed in GBM, and tightly correlated with poor prognosis, which is one of the transcription factors with the highest hazard ratio in GBM. Indeed, our genome-wide nascent RNA sequencing using GRO-seq demonstrated that YY2 promotes the transcriptional activation of all the enzymes in the canonical glycolysis pathway. Further functional study supported the role of YY2 in extracellular acidification and glucose consumption. Therefore, the current proposal will focus on studying the functions and mechanisms of YY2 in regulation of the Warburg effect in GBM, exploring the possibility of YY2 activity as a potential drug target for GBM.