Regulation of autophagy and mitophagy by HSV-G47∆ oncolytic virus in U251 glioblastoma cancer stem-like cells under hypoxic and normoxic niches

Aim: This research aimed to investigate the molecular targets of HSV-G47∆ oncolytic virus on autophagy and mitophagy pathways in U251 Glioblastoma cancer stem cells under hypoxic and normoxic tumor microenvironments. Methods: A quantitative PCR was performed to detect the expression levels of autophagy-related genes (BECN1, LAMP1, PERK, IFN-γ, p62, LC3) and mitophagy-related genes (MFN2, PINK1, PARKIN) in both normoxic and hypoxic microenvironments. The U251-GBMCSCs were infected with the HSV-G47∆ oncolytic virus at a multiplicity of infection (Optimized MOI) = 1 for 14 h. Results: Expression analysis showed different regulation of autophagy and mitophagy-related genes in U251 glioblastoma stem-like cells after HSV-G47Δ infection. Among autophagy markers, IFN-γ, P62, PERK, and LC3 showed significant changes, while mitophagy-related genes such as MFN2, PINK1, and PARKIN were also affected. Under low-oxygen conditions, PERK, INF-γ, LC3, MFN2, PINK1, and PARKIN were noticeably downregulated. In contrast, the genes, including P62, LC3, IFN-γ, and PARKIN, were significantly upregulated under normoxic conditions. Conclusions: HSV-G47Δ has a more substantial regulatory effect on both autophagy and mitophagy pathways under low oxygen compared to normal oxygen levels, indicating that glioblastoma stem-like cells are more susceptible in low-oxygen environments.

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