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

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.

Long non-coding RNA LUCAT1 regulates the RAS pathway to promote the proliferation and invasion of malignant glioma cells through ABCB1.

Long non-coding RNAs (lncRNAs) are closely related to the occurrence and development of tumors and have gradually become a hot topic in the field of glioma research in recent years. In this study, the role of lung cancer associated transcript 1 (lncRNA LUCAT 1) in glioma occurrence and development, as well as its possible regulatory mechanism, was explored. We utilized the gene chip technology in the preliminary experiment, and based on the experiment results, selected LUCAT1（NONHSAT102745）, which was significantly upregulated in glioma, and ATP-binding cassette Subfamily B member l (ABCB1), which was significantly down-regulated in co-expression analysis, for study. Next, the expression of LUCAT1 and ABCB1 in cells and tissues was immediately evaluated. Subsequently, the cells were transfected with scrambled siRNA, LUCAT1-siRNA/ABCB 1-siRNA, or overexpressed LUCAT1/ABCB1 plasmid + RAS signaling pathway inhibitor-farnesylthiosalicylic acid (FTS). By comparing with the normal combination negative control group, the cell proliferation and invasion ability were evaluated. Finally, subcutaneous tumor formation experiments in the nude mice confirmed the association between LUCAT1 and ABCB1 and RAS signaling pathways. The expression of LUCAT 1 was up-regulated with an increase in WHO grade, and the lncRNA-mRNA co-expression analysis showed that the expression of ABCB1 was low. LUCAT 1 gene knockout reduced the mRNA and protein levels of Ras signaling pathway related factors (Ras, Raf-1, p-AKT, and p-ERK) as regulating ABCB1 expression and inhibiting the ability of tumor in proliferation and invasion no matter in vitro or in vivo. For overexpressing of LUCAT 1, the opposite was true. After we knocked out ABCB1, the LUCAT1 expression was reversely regulated while the level of RAS signaling pathway related factors increased, and the ability of tumors in proliferation and invasion was enhanced. The abnormal LUCAT1 expression affected the biological behaviors of glioma cells, such as proliferation, invasion, etc. by regulating ABCB1 and promoting the activation of the RAS signaling pathway. This provided a new drug target and therapeutic approach for gene therapy of glioma, which is expected to significantly improve the prognosis of relevant patients.