Homeobox B8 Targets Sterile Alpha Motif Domain-Containing Protein 9 and Drives Glioma Progression

Gliomas are the most commonly occurring tumors of the central nervous system. Glioblastomamultiforme (GBM) is the most malignant and aggressive brain cancerin adults. Further understanding of the mechanisms underlying the aggressive nature of GBM is urgently needed. Here we identified homeoboxB8 ( HOXB8), a member of the homeoboxfamily, as a crucial contributor to the aggressiveness of GBM. Data mining of publicly accessible RNA sequence datasets and our patient cohorts confirmed a higher expression of HOXB8in the tumor tissue of GBM patients, and a strong positive correlation between the expression level and pathological grading of tumors and a negative correlation between the expression level and the overall survival rate. We next showed that HOXB8promotes the proliferation and migration of glioblastomacells and is crucial for the activation of the PI3K/AKT pathway and expression of epithelial–mesenchymal transition-related genes, possibly through direct binding to the promoter of SAMD9 ( Sterile Alpha MotifDomain-Containing Protein 9) and activating its transcription. Collectively, we identified HOXB8as a critical contributor to the aggressiveness of GBM, which provides insights into a potential therapeutic target for GBM and opens new avenues for improving its treatment outcome.