Histone acetyltransferase HAT1 drives malignant progression in lower-grade glioma: reshaping the immune microenvironment and molecular mechanisms

Zhi Sha; Zongye Zhang; Han Liu; Zhenxing Hou; Dongdong Wang; Zhichang Zhang; Yanzheng Gao; Zhendong Liu

doi:10.1016/j.neuroscience.2026.02.011

Histone acetyltransferase HAT1 drives malignant progression in lower-grade glioma: reshaping the immune microenvironment and molecular mechanisms

Neuroscience. 2026 Feb 14:S0306-4522(26)00100-4. doi: 10.1016/j.neuroscience.2026.02.011. Online ahead of print.

Authors

Zhi Sha¹, Zongye Zhang¹, Han Liu², Zhenxing Hou³, Dongdong Wang¹, Zhichang Zhang¹, Yanzheng Gao⁴, Zhendong Liu⁵

Affiliations

¹ Zhengzhou University People's Hospital, Henan Provincial People's Hospital, China.
² Henan Medical University, Henan Provincial People's Hospital, China.
³ Henan University People's Hospital, Henan Provincial People's Hospital, China.
⁴ Department of Surgery of Spine and Spinal Cord, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 471003, China. Electronic address: yanzhenggaohn@163.com.
⁵ Department of Surgery of Spine and Spinal Cord, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 471003, China. Electronic address: superliuyisheng@outlook.com.

PMID: 41698431
DOI: 10.1016/j.neuroscience.2026.02.011

Abstract

Background: HAT1's role in lower-grade glioma (LGG) malignancy and mechanisms is unclear.

Methods: Multi-omics analysis (TCGA/CGGA transcriptomics, single-cell/spatial transcriptomics, IHC/RT-qPCR) of 906 LGG patients assessed HAT1 expression, prognosis, pathways, immune infiltration, and cellular localization. Molecular docking screened HAT1-targeting drugs.

Results: HAT1 was significantly upregulated in LGG vs. normal brain, correlating with IDH-wildtype status, recurrence, and worse overall survival (independent risk factor). It specifically enriched malignant cell regions. HAT1 overexpression activated cell cycle, adherens junctions, and RIG-I-like signaling. It promoted immune cell infiltration and checkpoint expression. Top FDA-approved compounds with strong binding affinity were identified.

Conclusions: HAT1 drives LGG malignancy by remodeling the immune microenvironment and activating key oncogenic pathways. Its spatial enrichment in malignant niches and druggability provide a novel basis for targeted-immunotherapy combinations.

Keywords: Bioinformatics; HAT1; Immune microenvironment; LGG.