Journal Article

Functional analysis and verification of GYG2 in oncolytic virus-infected glioma

Zhang, Yinghui, Dong, Ying, Wang, Songquan, Wang, Chujun, Zhou, Jia, Yin, Xiaofeng

2025

Overview

Background Oncolytic virus has emerged as a promising candidate against tumors by infecting and killing cancer cells. In addition to poor prognosis of patients with glioma, the exact mechanisms driving the oncolytic virus therapy in glioma remain poorly understood. Methods We employed Enterovirus A71 (EV-A71)-based dataset (GSE136330), vesicular stomatitis virus (VSV)-M51-based dataset (GSE166914) and TCGA-glioma cohort to identify potential candidate gene after oncolytic virus infection. Then we investigated the correlation between glycogenin-2 (GYG2) and crucial outcomes such as clinical features, overall survival, tumor microenvironment. GO enrichment and GSEA analysis were performed to identify GYG2-coexpressed genes and potential regulatory pathways in glioma. The expression level of GYG2 in glioma tissues and cells was evaluated by qRT-PCR. Loss- and gain-of-function and rescue studies were used to explore the functional effect of GYG2 on glioma cell growth and apoptosis in VSV-M51-infected cells. Results Bioinformatics analysis show that GYG2 is downregulated after VSV-M51 or EV-A71 infection in glioma T98 cells. High expression of GYG2 in glioma is associated with high WHO grade and poor prognosis. In addition, GYG2 expression is linked with immune cell infiltration and immune microenvironment in glioma. GYG2 and its co-expressed protein are involved in regulating integrin 1 pathway and aurora B pathway in glioma. Downregulating GYG2 inhibits glioma cell growth and facilitates tumor cell apoptosis. Importantly, VSV-M51 infection promotes glioma cell apoptosis by downregulating GYG2. Conclusions Overall, this study advances our knowledge on the mechanisms of oncolytic virus infection and highlights a novel anti-apoptotic effect of GYG2 in glioma, further supporting it as an oncolytic virus target for therapy.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Analysis / Apoptosis / Apoptosis - genetics / Aurora B protein / Bioinformatics / Biomedical and Life Sciences / Biomedicine / Blood-brain barrier / Brain cancer / Brain Neoplasms - genetics / Brain Neoplasms - metabolism / Brain Neoplasms - pathology / Brain Neoplasms - therapy / Brain tumors / Cancer Research / Cancer therapies / Care and treatment / Cell growth / Cell Line, Tumor / Cell Proliferation / Chemotherapy / Datasets / Drug resistance / Enterovirus A, Human / Female / Flow cytometry / Gene expression / Gene Expression Regulation, Neoplastic / Genetic aspects / Glioma / Glioma - genetics / Glioma - metabolism / Glioma - mortality / Glioma - pathology / Glioma - therapy / Glioma - virology / Glioma cells / Gliomas / Health aspects / Health Promotion and Disease Prevention / Humans / Infections / Medicine/Public Health / Metastases / Oncology / Oncolysis / Oncolytic Virotherapy - methods / Oncolytic virus / Oncolytic Viruses / Plasmids / Prognosis / Reagents / Software / Stomatitis / Surgical Oncology / Tumor Microenvironment / Vesicular stomatitis virus / Viruses