Transcription factor SP1-Mediated Upregulation of B-Myb Promotes Glioma Aggression Through Transcriptomic Mechanism

Background Given the limited therapeutic options for gliomas, identifying molecules with therapeutic potential remains critical. This study aimed to investigate the functional significance and regulatory mechanisms of B-Myb in glioma progression. Methods B-Myb expression was assessed in glioma tissues through multimodal analyses (qRT-PCR, Western blotting, immunohistochemistry, and immunofluorescence). Prognostic relevance was evaluated in 325 glioma patients. Functional consequences of B-Myb modulation were examined via overexpression and knockdown approaches, with subsequent evaluation of proliferation, invasion, and DNA damage responses. Transcriptional regulation of B-Myb by SP1 was validated using chromatin immunoprecipitation (ChIP) and luciferase reporter assays. Results B-Myb was markedly upregulated in gliomas, with elevated expression correlating with advanced histopathological grades and reduced patient survival ( P  < 0.01). Functionally, B-Myb overexpression promoted tumor cell proliferation and invasion while suppressing DNA damage responses, whereas its knockdown reversed these phenotypes. Mechanistically, SP1 activated B-Myb transcription by binding to its promoter, thereby driving glioma malignancy. Vorinostat, a histone deacetylase inhibitor, demonstrated potent antitumor effects by suppressing B-Myb expression in preclinical models. Conclusions Our findings establish B-Myb as a clinically relevant oncoprotein in gliomas, with its expression driven by SP1-mediated transcriptional activation. The therapeutic efficacy of Vorinostat via B-Myb targeting highlights its potential for clinical translation. These results position B-Myb as both a prognostic biomarker and a promising therapeutic target for glioma management.