Oncolytic Virus Infection Modulates Lysine Acetyltransferase in Gliomas: Comprehensive Analysis and Experimental Validation of KAT8 in Glioma

ABSTRACT Oncolytic virotherapy, which uses engineered viruses to selectively target tumour cells, has emerged as a potential treatment in glioma. However, how oncolytic virus infection modulates lactylation enzymes in gliomas remains unclear. The RNA‐seq data after oncolytic virus EV‐A71 infection on glioma cells was analysed to screen and lysine acetyltransferase 8 (KAT8) was selected. We analysed KAT8 expression in glioma tissues using data from The Cancer Genome Atlas (TCGA) and Genotype‐Tissue Expression (GTEx) databases. Associations between KAT8 expression and clinicopathological features were evaluated. Kaplan–Meier survival analysis and Cox regression models were used to assess the prognostic value of KAT8. Functional annotation analyses were performed to explore the KAT8‐related biological processes. Single‐cell RNA‐sequencing data were analysed to investigate cell‐type‐specific KAT8 expression. In vitro experiments were conducted to validate the effects of KAT8 knockdown on apoptosis in glioma cells. KAT8 was among the top 5 down‐regulated genes in glioma cells after oncolytic viruses EV‐A71 infection. KAT8 was significantly overexpressed in glioma tissues compared to normal brain tissues, with higher expression in lower‐grade gliomas. High KAT8 expression was associated with 1p19q co‐deletion, IDH mutation, and younger patient age. Notably, high KAT8 expression correlated with better overall survival in grade IV gliomas. Functional analyses revealed KAT8's involvement in neuronal development, mRNA processing, and apoptosis regulation. Single‐cell sequencing data revealed a negative correlation between KAT8 expression and apoptosis in glioblastoma cells. In vitro experiments confirmed the increased apoptosis in glioma cell lines following KAT8 knockdown. Our findings suggest that the regulatory pathway of oncolytic virus infection for lactylation enzymes may be a key pathway affecting gliomas. These findings highlight KAT8 as a potential prognostic biomarker and therapeutic target for gliomas.