Interferon-gamma regulates the progression of neuroblastoma cells through interferon-regulatory factor-1

Objective: This study aimed to elucidate the in fl uence of IFN-gamma (IFN- gamma) in neuroblastoma (NB) cells and reveal its potential underlying molecular mechanism. Methods: The Cell Counting Kit-8, Transwell apparatus, and fl ow cytometry were employed to assess cellular viability, migratory capacity, invasive potential, and apoptotic rates, respectively. RNA-seq combined with bioinformatics analysis revealed differentially expressed genes (DEGs) and their possible biological functions. Protein levels were determined by western blot analysis. Results: IFN- gamma treatment resulted in diminished cell viability, mitigated migratory and invasive capabilities, and augmented apoptotic activity in the SK-N-BE (2) cell line, whereas it exhibited the opposite effect in SH-SY5Y cells. Furthermore, interferon regulatory factor 1 (IRF-1) was the common DEG in both IFN- gamma-treated SK-N-BE (2) and SH-SY5Y cells. Additionally, we found that it was underexpressed in NB tissues. The depletion of IRF-1 promoted the progression of both SK-N-BE (2) and SH-SY5Y cells. Moreover, IRF-1 knockdown effectively counteracted the effects of IFN- gamma on SK-N-BE (2) cells, while exacerbating them in SH-SY5Y cells. Conclusion: This study veri fi ed that IFN- gamma exerted a distinct role in both N-Myc-and non-N-Myc-ampli fi ed NB cells, partially by mediating the expression of IRF-1, suggesting that it may serve as a potent agent for treating patients with NB.