PFKFB4在脑胶质瘤糖代谢重编程中的作用及分子调控机制

脑胶质瘤是一种高发病率，高恶性程度，高复发率，预后极差的神经上皮肿瘤。胶质瘤的生长需要充足的营养物质和能量供给。肿瘤代谢特征已成为新的肿瘤恶性表型，糖代谢重编程是其主要体现之一。胶质瘤糖代谢相关机制的研究对该疾病的治疗及预后有重要意义。近期研究提示PFKFB4具有蛋白激酶的新特性，可促进肿瘤生长及转移，但其在转录调控肿瘤糖代谢重编程中的作用尚不清楚。胶质瘤中PFKFB4表达上调与预后密切相关。我们前期工作中发现其与肿瘤糖代谢重编程重要因子HIF-1α的表达存在正相关关系。本项目拟在前期工作基础上，通过临床标本检测及体外细胞实验探明PFKFB4与胶质瘤的临床相关性及在调控糖代谢重编程和线粒体功能中的作用及相关信号通路，并在动物模型中验证和评价PFKFB4抑制剂的临床应用前景。本研究可阐明PFKFB4在胶质瘤糖代谢重编程中的作用及机制，以期发现调控糖代谢的新靶点，为胶质瘤的综合治疗提供新依据。

Glioma is a neuroepithelial neoplasm with high morbidity, high malignancy, high recurrence, and poor prognosis. The growth of glioma requires adequate nutrients and energy supply. Tumor metabolism has become a new malignant phenotype of tumors, and reprogramming of glucose metabolism in tumor cells is one of its main manifestations. The research on the mechanism of glucose metabolism changes in glioma is of great significance for the treatment and prognosis of this disease. Recent studies suggest that PFKFB4 has a new property of protein kinase that promote tumor growth and metastasis. However, its role in tumor glucose metabolism reprogramming through transcriptional regulation remains unclear. In gliomas, the expression of PFKFB4 is significantly up-regulated and is closely related to the prognosis of patients. In our previous work, we also found a positive correlation with the expression of HIF-1α, an important factor involved in tumor glucose metabolism reprogramming. Based on our previous study, our current study is to explore the clinical correlation between PFKFB4 and glioma, the role of PFKFB4 in the regulation of glucose metabolism reprogramming and mitochondrial function, as well as the relevant signal pathways through clinical specimen detection and in vitro cell experiments. Finally, the experimental results will be validated in animal models and the clinical potential of PFKFB4-specific inhibitors will be evaluated. Collectively, our investigation here can elucidate the role and mechanism of PFKFB4 in glioma glucose metabolism reprogramming，in order to find new targets for regulating glioma glucose metabolism, and provide a new theoretical basis for the comprehensive treatment of glioma.