Glioblastoma (GBM) is the most common and fatal type of primary malignant tumours in the central nervous system. Cytokines such as interleukins (ILs) play an important role in GBM progression. Our present study found that IL-24 is down-regulated in GBM cells. Recombinant IL-24 (rIL-24) can suppress the in vitro migration and invasion of GBM cells while increase its chemo-sensitivity to temozolomide (TMZ) treatment. rIL-24 negatively regulates the expression of Zeb1, one well known transcription factors of epithelial to mesenchymal transition (EMT) of cancer cells. Over expression of Zeb1 can attenuate IL-24-suppressed malignancy of GBM cells. Mechanistically, IL-24 decreases the protein stability of Zeb1 while has no effect on its mRNA stability. It is due to that IL-24 can increase the expression of FBXO45, which can destabilize Zeb1 in cancer cells. Collectively, we reveal that IL-24 can suppress the malignancy of GBM cells via decreasing the expression of Zeb1. It suggests that targeted activation of IL-24 signals might be a potential therapy approach for GBM treatment.

中文翻译：

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IL-24 通过破坏 Zeb1 来抑制人胶质母细胞瘤细胞的恶性肿瘤

胶质母细胞瘤（GBM）是中枢神经系统中最常见和致命的原发性恶性肿瘤。细胞因子如白细胞介素 (IL) 在 GBM 进展中起重要作用。我们目前的研究发现 IL-24 在 GBM 细胞中下调。重组 IL-24 (rIL-24) 可以抑制 GBM 细胞的体外迁移和侵袭，同时增加其对替莫唑胺 (TMZ) 治疗的化学敏感性。rIL-24 负向调节 Zeb1 的表达，Zeb1 是一种众所周知的癌细胞上皮间质转化 (EMT) 转录因子。Zeb1 的过度表达可以减弱 IL-24 抑制的 GBM 细胞恶性肿瘤。从机制上讲，IL-24 降低了 Zeb1 的蛋白质稳定性，而对其 mRNA 稳定性没有影响。这是由于IL-24可以增加FBXO45的表达，它可以破坏癌细胞中的 Zeb1。总的来说，我们揭示了 IL-24 可以通过降低 Zeb1 的表达来抑制 GBM 细胞的恶性肿瘤。这表明 IL-24 信号的靶向激活可能是 GBM 治疗的潜在治疗方法。