Newcastle disease virus promotes pyroptosis in medulloblastoma cells by regulating interferon-gamma-mediated guanylate-binding protein 1 expression and activating caspase-4.

Abstract

Objective: The literature has reported that Newcastle disease virus (NDV) can have inhibitory effects on various tumors. This study aims to investigate the mechanism by which NDV induces pyroptosis in medulloblastoma (MB) cells.

Material and methods: We treated MB cell lines Daoy and D283 with NDV or recombinant interferon-gamma (IFN-g) proteins. Guanylate-binding proteins (GBPs) were measured using real-time quantitative polymerase chain reaction. Small interfering RNA-specific targeting GBP1 was transfected into MB cells. Apoptosis was assessed using Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nucleoside nick end labeling and flow cytometry assays. Pyroptosis-related proteins, including caspase-4, caspase-1, and gasdermin D (GSDMD), were detected using Western blotting.

Results: Bioinformatics analysis revealed that GBP family genes and interferon-related genes might be responsive to NDV stimulation in MB cells. Treatment with NDV resulted in increased IFN-g levels and upregulated GBP expression, particularly GBP1. In addition, IFN-g treatment induced GBP1 expression and enhanced cell apoptosis. GBP1 knockdown attenuated the decreased cell proliferation and increased cell apoptosis induced by NDV in MB cells. GBP1 overexpression upregulated the expression of pyroptosis-related proteins, including caspase-4, caspase-1, and GSDMD, subsequently leading to inhibition of cell proliferation and an increase in cell apoptosis levels. The silencing of caspase-4 confirmed the regulatory role of GBP1 in MB cell pyroptosis.

Conclusion: Our findings suggest that NDV elevates IFN-g and GBP1 expression in MB cells, potentially contributing to caspase-4-mediated pyroptosis activation.