目前肿瘤细胞代谢已成为肿瘤研究的热点。我们预实验发现：下调PKM2和上调let-7a能有效抑制胶质瘤糖酵解和生长；上调let-7a可抑制靶基因KRAS和MYC及下游HnRNPA1与PKM2表达；敲低HnRNPA1能下调PKM2而上调let-7a。据此提出假说：let-7a/KRAS/MYC/HnRNPA1环路调控PKM2信号在胶质瘤糖代谢与生长中发挥重要作用。本课题拟以EGFR、PTEN与IDH1不同状态的胶质瘤细胞为模型，以转录调控、转录后调控、基因回复等为手段,全面分析let-7a/KRAS/MYC/HnRNPA1环路调控PKM2的网络及其对胶质瘤糖代谢与生长的影响，分析关键节点在胶质瘤分子诊断、预后判断及靶向治疗中的作用。本课题将揭示不同遗传背景下基于let-7a/KRAS/MYC/HnRNPA1反馈环路的PKM2网络对胶质瘤糖代谢与生长的作用与机理，为寻找胶质瘤新治疗靶点奠定基础。

Up to now, tumor metabolism has become one of the hot topics in cancer research. Our data showed that down-regulation of PKM2 and up-regulation of let-7a inhibited glioma cell glycine metabolism and growth. Up-regulation of let-7a also reduced the expression of its target genes (KRAS and MYC) and the downstream genes (HnRNPA1 and PKM2). Further, reduction of HnRNPA1 inhibited PKM2 expression, whereas induced let-7a expression. Thus, we proposed the hypothesis that PKM2 regulation network based on let-7a/KRAS/MYC/HnRNPA1 feedback loop plays a key role in glioma glycine metabolism and growth. In the future study, we will choose glioma cells with different gene backgrounds (EGFR、PTEN and IDH1) as cell models and transcriptional regulation, posttranscriptional regulation and gene rescue as major methods, evaluate the effect of PKM2 regulation network based on let-7a/KRAS/MYC/HnRNPA1 feedback loop on glioma glycine metabolism and growth, further analyze the role of key notes in glioma molecular diagnosis, prognosis evaluation and targeting therapy. In conclusion, our finding will reveal the role and mechanism of PKM2 regulation network based on let-7a/KRAS/MYC/HnRNPA1 feedback loop in glioma glycine metabolism and growth, and provides more potential approaches for glioma treatment.