E2F2 drives glioma progression via PI3K/AKT in a PFKFB4-dependent manner.

Aims: The effects of PFKFB4 on glycolysis during the cancer progression has been investigated, while its role in glioma remains unclear. The present study evaluated the molecular mechanism of PFKFB4 in glycolysis of glioma progression.
Materials and Methods: The pan-cancer platform SangerBox was inquired to investigate the E2F2 expression in tumors. The E2F2 expression was studied by qRT-PCR and immunohistochemistry in collected glioma and normal brain tissues and by qRT-PCR and western blot in glioma cells. The relationship between the E2F2 expression in glioma tissues and patients' prognosis was analyzed. The cell malignant phenotype, glycolysis, growth and metastasis were examined by CCK-8, EdU, colony formation, flow cytometry, wound healing, Transwell assays, ELISA kits, and tumorigenesis and metastasis assays. Downstream targets of E2F2 were searched in hTFtarget, followed by pathway enrichment analysis. The expression of these targets and their correlation with E2F2 expression in gliomas were investigated through the GEPIA website. After ChIP and luciferase assays, the effect of the target on glioma was investigated.
Key Findings: E2F2 was overexpressed in glioma patients and predicted poor prognoses. E2F2 promoted cell proliferation, colony formation, DNA synthesis, migration, invasion and glycolysis, and inhibited apoptosis. Meanwhile, inhibition of E2F2 suppressed the growth and metastasis of gliomas. E2F2 elevated the PFKFB4 expression transcriptionally by binding to its promoter and activated PI3K/AKT pathway. The promotion of glioma metastasis and glycolysis by E2F2 was mitigated by PFKFB4 knockdown.
Significance: E2F2-mediated transcriptional enhancement of PFKFB4 expression regulated the phosphorylation of PI3K/AKT to promote glioma malignancy progression.
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