Extracellular Vesicles Derived from Glioma Stem Cells Affect Glycometabolic Reprogramming of Glioma Cells Through the miR-10b-5p/PTEN/PI3K/Akt Pathway.

ABSTRACT

OBJECTIVE: Glioma is one of the most prevalently diagnosed types of primary malignant brain tumors. Glioma stem cells (GSCs) are crucial in glioma recurrence. This study aims to elucidate the mechanism by which extracellular vehicles (EVs) derived from GSCs modulate glycometabolic reprogramming in glioma. METHODS: Xenograft mouse models and cell models of glioma were established and treated with GSC-EVs. Additionally, levels and activities of PFK1, LDHA, and FASN were assessed to evaluate the effect of GSC-EVs on glycometabolic reprogramming in glioma. Glioma cell proliferation, invasion, and migration were evaluated using MTT, EdU, Colony formation, and Transwell assays. miR-10b-5p expression was determined, with its target gene PTEN and downstream pathway PI3K/Akt evaluated. The involvement of miR-10b-5p and the PI3K/Akt pathway in the effect of GSC-EVs on glycometabolic reprogramming was tested through joint experiments. RESULTS: GSC-EVs facilitated glycometabolic reprogramming in glioma mice, along with enhancing glucose uptake, lactate level, and adenosine monophosphate-to-adenosine triphosphate ratio. Moreover, GSC-EV treatment potentiated glioma cell proliferation, invasion, and migration, reinforced cell resistance to temozolomide, and raised levels and activities of PFK1, LDHA, and FASN. miR-10b-5p was highly-expressed in GSC-EV-treated glioma cells while being carried into glioma cells by GSC-EVs. miR-10b-5p targeted PTEN and activated the PI3K/Akt pathway, hence stimulating glycometabolic reprogramming. CONCLUSION: GSC-EVs target PTEN and activate the PI3K/Akt pathway through carrying miR-10b-5p, subsequently accelerating glycometabolic reprogramming in glioma, which might provide new insights into glioma treatment.