
The study identifies G Protein Subunit Alpha O1 (GNAO1) as a critical regulator of neural differentiation in glioma stem-like cells (GSCs). GNAO1 expression was found to be lower in gliomas compared to normal neuronal tissues, and higher levels of GNAO1 were associated with better prognosis. Overexpression of GNAO1 promoted neural differentiation, reduced cell proliferation, and inhibited colony formation in GSCs. Mechanistically, GNAO1 facilitated TRIM21-mediated ubiquitination of CREB, leading to decreased HES1 expression and enhanced neuronal differentiation. In orthotopic GSC xenografts, GNAO1 adenovirus treatment reduced tumor cell proliferation and prolonged survival, with temozolomide enhancing these effects. These findings suggest that GNAO1 overexpression could serve as a potential therapeutic strategy to counteract malignant glioma progression and chemotherapy resistance.
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