Malignant Glioma is characterized by strong self-renewal potential and immature differentiation potential. The main reason is that malignant glioma holds key cluster cells, glioma stem cells (GSCs). GSCs contribute to tumorigenesis, tumor progression, recurrence, and treatment resistance. Interferon-beta (IFN-β) is well known for its anti-proliferative efficacy in diverse cancers. IFN-β also displayed potent antitumor effects in malignant glioma. IFN-β affect both GSCs and Neural stem cells (NSCs) in the treatment of gliomas. However, the functional comparison, similar or different effects of IFN-β on GSCs and NSCs are rarely reported. Here, we studied the similarities and differences of the responses to IFN-β between human GSCs and normal NSCs. We found that IFN-β preferentially inhibited GSCs over NSCs. The cell body and nucleus size of GSCs increased after IFN-β treatment, and the genomic analysis revealed the enrichment of the upregulated immune response, cell adhesion genes and down regulated cell cycle, ribosome pathways. Several typical cyclin genes, including cyclin A2 (CCNA2), cyclin B1 (CCNB1), cyclin B2 (CCNB2), and cyclin D1 (CCND1), were significantly downregulated in GSCs after IFN-β stimulation. We also found that continuous IFN-β stimulation after passage further enhanced the inhibitory effect. Our study revealed how genetic diversity resulted in differential effects in response to IFN-β treatment. These results may contribute to improve the applications of IFN-β in anti-cancer immunotherapy. In addition, these results may also help to design more effective pharmacological strategies to target cancer stem cells while protecting normal neural stem cells.

中文翻译：

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干扰素-β通过调节免疫反应和细胞周期相关信号通路抑制人胶质瘤干细胞生长

恶性胶质瘤的特点是具有很强的自我更新潜力和不成熟的分化潜力。主要原因是恶性胶质瘤拥有关键的簇细胞，胶质瘤干细胞（GSCs）。GSCs有助于肿瘤发生、肿瘤进展、复发和治疗抵抗。干扰素-β (IFN-β) 以其在多种癌症中的抗增殖功效而闻名。IFN-β 在恶性胶质瘤中也显示出有效的抗肿瘤作用。IFN-β 在胶质瘤治疗中影响 GSC 和神经干细胞 (NSC)。然而，很少报道 IFN-β 对 GSC 和 NSC 的功能比较、相似或不同的影响。在这里，我们研究了人类 GSC 和正常 NSC 对 IFN-β 反应的异同。我们发现 IFN-β 优先抑制 GSCs 而不是 NSCs。IFN-β 处理后 GSCs 的细胞体和细胞核大小增加，基因组分析显示上调的免疫反应、细胞粘附基因和下调的细胞周期、核糖体途径的富集。几种典型的细胞周期蛋白基因，包括细胞周期蛋白 A2 (CCNA2)、细胞周期蛋白 B1 (CCNB1)、细胞周期蛋白 B2 (CCNB2) 和细胞周期蛋白 D1 (CCND1)，在 IFN-β 刺激后在 GSCs 中显着下调。我们还发现传代后持续的 IFN-β 刺激进一步增强了抑制作用。我们的研究揭示了遗传多样性如何导致对 IFN-β 治疗的不同影响。这些结果可能有助于改善 IFN-β 在抗癌免疫治疗中的应用。此外，