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Here, it is found that hypoxia preferentially induces the actin\u2010binding protein, Transgelin (TAGLN), in GBM stem cells (GSCs). Mechanistically, TAGLN regulates HIF1\u03b1 transcription and stabilizes HDAC2 to deacetylate p53 and maintain GSC self\u2010renewal. To translate these findings into preclinical therapeutic paradigm, it is found that sodium valproate (VPA) is a specific inhibitor of TAGLN\/HDAC2 function, with augmented efficacy when combined with natural borneol (NB) in vivo. 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