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

作者：Xiaofeng Yin, Zhen Hao, Qi Liu, Rui Ding, Laizhao Chen, Mingliang Jin, Songquan Wang · 发表于：Journal of Cellular and Molecular Medicine · 年份：2025 · DOI：10.1111/jcmm.70558 · 被引用次数：4 · 研究领域：Virus-based gene therapy research、RNA Interference and Gene Delivery、CRISPR and Genetic Engineering

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 ne...