Transcriptome Changes in Glioma Cells upon Infection with the Oncolytic Virus VV-GMCSF-Lact
Dmitriy V Semenov1, Natalia S Vasileva1, Maya A Dymova1
1Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, Lavrentyev Avenue, 8, 630090 Novosibirsk, Russia.
Abstract:
Oncolytic virotherapy is a rapidly evolving approach that aims to selectively kill cancer cells. We designed a promising recombinant vaccinia virus, VV-GMCSF-Lact, for the treatment of solid tumors, including glioma. We assessed how VV-GMCSF-Lact affects human cells using immortalized and patient-derived glioma cultures and a non-malignant brain cell culture. Studying transcriptome changes in cells 12 h or 24 h after VV-GMCSF-Lact infection, we detected the common activation of histone genes. Additionally, genes associated with the interferon-gamma response, NF-kappa B signaling pathway, and inflammation mediated by chemokine and cytokine signaling pathways showed increased expression. By contrast, genes involved in cell cycle progression, including spindle organization, sister chromatid segregation, and the G2/M checkpoint, were downregulated following virus infection. The upregulation of genes responsible for Golgi vesicles, protein transport, and secretion correlated with reduced sensitivity to the cytotoxic effect of VV-GMCSF-Lact. Higher expression of genes encoding proteins, which participate in the maturation of pol II nuclear transcripts and mRNA splicing, was associated with an increased sensitivity to viral cytotoxicity. Genes whose expression correlates with the sensitivity of cells to the virus are important for increasing the effectiveness of cancer virotherapy. Overall, the results highlight molecular markers, biological pathways, and gene networks influencing the response of glioma cells to VV-GMCSF-Lact.
Insights
This study explored how VV-GMCSF-Lact oncolytic virus impacts glioma cells. It identified key gene expression changes, revealing molecular markers that influence cancer virotherapy effectiveness.
Area of Science:
- Oncolytic Virotherapy
- Molecular Biology
- Cancer Research
Background:
- Oncolytic virotherapy utilizes viruses to selectively target and destroy cancer cells.
- Glioma, a type of brain tumor, presents significant treatment challenges.
- Recombinant vaccinia virus VV-GMCSF-Lact is a novel agent explored for solid tumor treatment.
Purpose of the Study:
- To investigate the molecular effects of VV-GMCSF-Lact on human glioma cells.
- To identify gene expression patterns associated with sensitivity and resistance to VV-GMCSF-Lact.
- To uncover potential biomarkers for enhancing oncolytic virotherapy efficacy.
Main Methods:
- Transcriptome analysis of immortalized and patient-derived glioma cells post-infection with VV-GMCSF-Lact.
- Comparison of gene expression profiles in infected glioma cells versus non-malignant brain cells.
- Correlation analysis between gene expression levels and cellular sensitivity to viral cytotoxicity.
Main Results:
- VV-GMCSF-Lact infection commonly activated histone genes and upregulated inflammatory/interferon-gamma response pathways.
- Genes involved in cell cycle progression were downregulated post-infection.
- Upregulation of Golgi vesicle and protein transport genes correlated with reduced sensitivity, while mRNA splicing gene upregulation indicated increased sensitivity.
Conclusions:
- VV-GMCSF-Lact influences glioma cell biology by modulating key cellular processes.
- Specific gene expression profiles can predict glioma cell sensitivity to VV-GMCSF-Lact.
- Identifying these molecular markers is crucial for optimizing oncolytic virotherapy strategies in glioma treatment.
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