GBE1 Promotes Glioma Progression by Enhancing Aerobic Glycolysis through Inhibition of FBP1

SIMPLE SUMMARY: Due to the poor prognosis of glioma patients and the limitations of glioma treatment, our study aimed to find new targets for glioma on metabolic therapy. Our study reveals a role for glycogen branching enzyme 1 (GBE1) in regulating glioma initiation and progression. We found that the expression of GBE1 correlated with a poor prognosis in glioma patients. Moreover, GBE1 promotes glioma progression by enhancing aerobic glycolysis through the inhibition of fructose–bisphosphatase 1 (FBP1), which reveals GBE1 as a potential target for glioma therapy. ABSTRACT: Tumor metabolism characterized by aerobic glycolysis makes the Warburg effect a unique target for tumor therapy. Recent studies have found that glycogen branching enzyme 1 (GBE1) is involved in cancer progression. However, the study of GBE1 in gliomas is limited. We determined by bioinformatics analysis that GBE1 expression is elevated in gliomas and correlates with poor prognoses. In vitro experiments showed that GBE1 knockdown slows glioma cell proliferation, inhibits multiple biological behaviors, and alters glioma cell glycolytic capacity. Furthermore, GBE1 knockdown resulted in the inhibition of the NF-κB pathway as well as elevated expression of fructose-bisphosphatase 1 (FBP1). Further knockdown of elevated FBP1 reversed the inhibitory effect of GBE1 knockdown, restoring glycolytic reserve capacity. Furthermore, GBE1 knockdown suppressed xenograft tumor formation in vivo and conferred a significant survival benefit. Collectively, GBE1 reduces FBP1 expression through the NF-κB pathway, shifting the glucose metabolism pattern of glioma cells to glycolysis and enhancing the Warburg effect to drive glioma progression. These results suggest that GBE1 can be a novel target for glioma in metabolic therapy.