The oncogenic effects of NFYC were partially reversed by KLF1 knockdown, and <i>vice versa</i>.<h4>Conclusion</h4>This study reveals a novel hierarchical transcriptional pathway in which NFYC regulates KLF1, which in turn activates LDHA, driving aerobic glycolysis and tumor progression in GBM. This evidence concerns the gene LDHA and glioblastoma.