PFKFB4 Interference Regulates Mitochondrial Membrane Fusion and Affects Glioma Proliferation and Apoptosis

Abstract

Background: Fructose-2,6-biphosphatase 4 (PFKFB4) is a key enzyme in glucose metabolism, and its differential expression is closely related to the occurrence and development of tumors. However, the related molecular mechanisms in glioblastoma(GBM) remain unclear. Methods: Firstly, the expression of PFKFB4 in normal and GBM tissues was analyzed by bioinformatics in The Cancer Genome Atlas (TCGA) database, and the relationship between PFKFB4 and survival was analyzed. Then detected the expression of PFKFB4 in tissues and cells of glioma. After PFKFB4 Interference, observed the proliferation by CCK8 and EDU, apoptosis of U87 cells by flow cytometry. the content of ATP and mitochondrial membrane function were detected. The possible interaction mechanism between PFKFB4 and mitochondria was analyzed by bioinformatics and verified by qPCR and Western blotting(WB). Finally, the experiment of subcutaneous tumor formation in nude mice was verified.Results: Our study found that PFKFB4 is highly expressed in glioma tissues and cell lines. High expression levels are associated with a poor prognosis. In addition, PFKFB4 inhibition attenuates the proliferation and mitochondrial function of cancer cells promotes apoptosis, and can also reduce ATP levels. Further studies showed that PFKFB4 affects the metabolic reprogramming of gliomas by regulating mitochondrial membrane fusion, Regulating the protein expression of mitofusin 1(MFN1), mitofusin 2(MFN2), opticatrophy-1(OPA1). Animal studies verify these results.Conclusion: PFKFB4 may be a potential therapeutic target for glioma.