Nuclear factor IX promotes glioblastoma development through transcriptional activation of Ezrin.,Oncogenesis

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Nuclear factor IX promotes glioblastoma development through transcriptional activation of Ezrin.
Oncogenesis ( IF 5.9 ) Pub Date : 2020-04-14 , DOI: 10.1038/s41389-020-0223-2
Zhuohao Liu ₁ , Ruixiang Ge ₂ , Jiayi Zhou ₃ , Xinzhi Yang ₁ , Kenneth King-Yip Cheng ₄ , Jingli Tao ₅ , Dinglan Wu ₃ , Jie Mao _{1,

2}

Affiliation

Enhanced migration is pivotal for the malignant development of glioblastoma (GBM), but the underlying molecular mechanism that modulates the migration of the GBM cells remains obscure. Here we show that nuclear factor IX (NFIX) is significantly upregulated in human GBM lesions compared with normal or low-grade gliomas. NFIX deficiency impairs the migration of GBM cells and inhibits the tumor growth in the hippocampus of immunodeficient nude mice. Mechanistically, NFIX silencing suppresses the expression of Ezrin, a protein that crosslinks actin cytoskeleton and plasma membrane, which is also positively correlated with GBM malignancy. NFIX depletion induced migration inhibition of GBM cells can be rescued by the replenishment of Ezrin. Furthermore, we identify a NFIX response element (RE) between -840 and -825 bp in the promoter region of the Ezrin gene. Altogether, our findings show, for the first time that NFIX can transcriptionally upregulate the expression of Ezrin and contribute to the enhanced migration of GBM cells, suggesting that NFIX is a potential target for GBM therapy.

中文翻译：

核因子IX通过Ezrin的转录激活促进胶质母细胞瘤的发展。

迁移的增强对于胶质母细胞瘤（GBM）的恶性发展至关重要，但是调节GBM细胞迁移的潜在分子机制仍然不清楚。在这里，我们显示与正常或低度神经胶质瘤相比，人GBM病变中的核因子IX（NFIX）明显上调。NFIX缺乏会损害GBM细胞的迁移并抑制免疫缺陷裸鼠海马中的肿瘤生长。从机制上讲，NFIX沉默抑制Ezrin的表达，Ezrin是一种与肌动蛋白细胞骨架和质膜交联的蛋白质，也与GBM恶性肿瘤呈正相关。NFIX耗尽诱导的GBM细胞迁移抑制可以通过补充Ezrin来挽救。此外，我们在Ezrin基因的启动子区域鉴定了一个介于-840和-825 bp之间的NFIX反应元件（RE）。总而言之，我们的研究结果首次显示NFIX可以转录上调Ezrin的表达并有助于提高GBM细胞的迁移，这表明NFIX是GBM治疗的潜在靶标。

更新日期：2020-04-14

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