BACKGROUND

Gliomas are highly aggressive brain tumors with complex metabolic and molecular alterations. The role of glycolysis in glioma progression and its regulation by hypoxia remain poorly understood. This study investigated the function of glycogen phosphorylase L () in glioma and its interaction with glycolytic pathways under hypoxic conditions.

METHODS

Differential expression analysis was conducted using The Cancer Genome Atlas (TCGA) glioma and GSE67089 datasets, revealing significant changes in the expression of genes. A prognostic risk model incorporating was built by univariate and multivariate Cox regression analyses. The impacts of on glioma cell proliferation, glycolysis, apoptosis, and metabolic activities were evaluated by assays. Additionally, the influences of hypoxia and hypoxia-inducible factor 1-alpha () on expression were evaluated.

RESULTS

Our prognostic prediction model showed a C-index of 0.76 [95% confidence interval (CI): 0.70-0.82], indicating a good predictive accuracy of the model. In addition, genetic predictors included in the nomogram included PYGL, HIF1α, and other genes associated with the glycolytic pathway. Differential expression analysis identified as a key gene associated with glioma survival. expression was significantly upregulated in glioma cells. knockdown inhibited cell invasion, proliferation, migration, and colony formation and enhanced apoptosis via modulation of Bcl-2, caspase-3, and Bax. Glycolysis was impaired in -knockdown cells, as indicated by increased glycogen levels and a reduced extracellular acidification rate (ECAR), adenosine triphosphate (ATP) levels, lactate levels, and PKM2 and LDHA expression. overexpression promoted glycolysis and cell viability, which was counteracted by 2-deoxy-D-glucose (2-DG). Hypoxia-induced expression was regulated by , underscoring the interplay between the hypoxia and glycolysis pathways.

CONCLUSIONS

is a crucial regulator of glycolysis in gliomas and contributes to tumor progression under hypoxic conditions. Targeting and its associated metabolic pathways may offer new therapeutic strategies for glioma treatment.