Multi-omics characterization identifies HAT1 as a key regulator of proliferation and therapeutic sensitivity in glioblastoma

Glioblastoma (GBM) is a highly malignant brain tumor with an extremely poor prognosis, highlighting the urgent need to identify novel diagnostic and therapeutic targets. Histone acetyltransferase 1 ( HAT1 ) serves as a critical epigenetic regulator. In this study, we systematically investigated the expression characteristics, biological functions, and clinical significance of HAT1 in GBM through multi-omics analysis combined with in vitro and in vivo functional experiments. We found that HAT1 is significantly upregulated in GBM and may act as a promising diagnostic and prognostic biomarker. Functionally, HAT1 maintains genomic stability by facilitating DNA damage repair, cell cycle progression, and metabolic reprogramming, thereby promoting the malignant progression of GBM. Moreover, HAT1 participates in remodeling the tumor immune microenvironment. In vitro, genetic knockdown or pharmacological inhibition of HAT1 markedly suppressed GBM cell proliferation and induced tumor DNA damage. In vivo experiments further validated that HAT1 inhibition effectively impeded GBM tumor growth. Notably, pharmacological inhibition of HAT1 enhances the antitumor efficacy of Temozolomide (TMZ) and Niraparib in GBM cells. In summary, HAT1 is a key epigenetic regulator driving GBM progression, which can serve as a novel prognostic biomarker and a viable therapeutic target for combined treatment strategies, providing new insights for the precise treatment of GBM.