Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin150001, People's Republic of China.
Department of Neurosurgery, Heilongjiang Provincial Hospital, Harbin150030, People's Republic of China.
Biol Chem. 2021 Apr 26;402(7):839-848. doi: 10.1515/hsz-2020-0373. Print 2021 Jun 25.
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 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.
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（ILs）在 GBM 进展中发挥重要作用。我们目前的研究发现，IL-24 在 GBM 细胞中下调。重组白细胞介素 24（rIL-24）可抑制 GBM 细胞的迁移和侵袭，同时增加其对替莫唑胺（TMZ）治疗的化疗敏感性。rIL-24 负调控 Zeb1 的表达，Zeb1 是癌细胞上皮间质转化（EMT）的一个众所周知的转录因子。Zeb1 的过表达可以减弱 IL-24 抑制 GBM 细胞恶性的作用。在机制上，IL-24 降低了 Zeb1 的蛋白稳定性，而对其 mRNA 稳定性没有影响。这是因为 IL-24 可以增加 FBXO45 的表达，从而使癌细胞中的 Zeb1 不稳定。总之，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。这表明靶向激活 IL-24 信号可能是 GBM 治疗的一种潜在治疗方法。
