Effect of Glioma Stem Cells-derived Extracellular Vesicles on Glucose Metabolism Reprogramming in Glioma via the miR-26a/KLF4/PI3K/Akt axis

Abstract BackgroundGlioma represents one of the most intractable malignancy occurring in central nervous system. Glioma stem cells (GSCs) constitute a type of seed cells with self-renewal and multi-directional differentiation potentials. This study investigated the mechanism of GSCs-derived extracellular vesicles (EVs) in glucose metabolism reprogramming in glioma.MethodsGlioma cells were treated with different concentrations (10, 20 and 30 μg/mL) of GSCs-EVs. Glucose consumption and lactic acid and adenosine triphosphate (ATP) production were measured and expressions of key enzymes in glycolysis pathway (PFK1, HK2 and PKM2) were detected. The proliferation, invasion and migration of glioma cells were measured. miR-26a expression in GSCs-EVs-treated cells was detected. The targeting relationship between miR-26a and KLF4 was predicted and verified. The phosphorylation levels of PI3K and Akt were detected. Glioma cells were co-incubated with GSCs-EVs and pcDNA-KLF4 to verify the role of PI3K/Akt pathway in glucose metabolism reprogramming.ResultsGlucose consumption and lactic acid and ATP production were promoted, and expressions of PFK1, HK2 and PKM2 were increased in GSCs-EVs-treated cells. GSCs-EVs facilitated proliferation, invasion and migration of glioma cells. miR-26a expression was enhanced in GSCs-EVs-treated cells. GSCs-EVs carried miR-26a into glioma cells and promoted glucose metabolism reprogramming. miR-26a inhibitor reduced the promoting effect of GSCs-EVs on glucose metabolism reprogramming. miR-26a repressed KLF4 expression and activated the PI3K/Akt pathway in glioma cells.ConclusionmiR-26a carried by GSCs-EVs promoted glucose metabolism reprogramming in glioma via targeting KLF4 and activating the PI3K/Akt pathway. This study may offer new insights for targeted intervention of glioma.