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Functional analysis and verification of GYG2 in oncolytic virus-infected glioma
Ying Dong1, Songquan Wang1, Chujun Wang1
1Department of neurosurgery, Second Hospital of Shanxi Medical University, Taiyuan, 030001, China.
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.
Insights
Glycogenin-2 (GYG2) is downregulated by oncolytic viruses in glioma, inhibiting cancer cell growth and promoting apoptosis. This finding reveals GYG2 as a potential therapeutic target for glioma treatment.
Area of Science:
- Oncolytic virology
- Cancer biology
- Molecular oncology
Background:
- Oncolytic viruses offer a promising strategy for cancer treatment by selectively infecting and destroying tumor cells.
- The precise mechanisms of oncolytic virus therapy in glioma, a cancer with a poor prognosis, are not fully understood.
Purpose of the Study:
- To identify genes involved in oncolytic virus infection in glioma.
- To investigate the role of glycogenin-2 (GYG2) in glioma progression and its response to oncolytic virus therapy.
Main Methods:
- Utilized Enterovirus A71 (EV-A71) and vesicular stomatitis virus (VSV)-M51 datasets, alongside TCGA-glioma cohort data.
- Analyzed the correlation of GYG2 expression with clinical features, survival, and tumor microenvironment.
- Conducted gene ontology (GO) enrichment, gene set enrichment analysis (GSEA), qRT-PCR, and loss/gain-of-function studies.
Main Results:
- GYG2 expression was downregulated in glioma cells following VSV-M51 or EV-A71 infection.
- High GYG2 expression correlated with advanced WHO grade, poor prognosis, and altered immune microenvironment in glioma.
- Downregulating GYG2 inhibited glioma cell proliferation and enhanced apoptosis, particularly during VSV-M51 infection.
Conclusions:
- Oncolytic virus infection of glioma promotes apoptosis through the downregulation of GYG2.
- GYG2 exhibits a novel anti-apoptotic role in glioma, positioning it as a potential therapeutic target for oncolytic virus therapy.
