Liu Zhuohao, Ge Ruixiang, Zhou Jiayi, Yang Xinzhi, Cheng Kenneth King-Yip, Tao Jingli, Wu Dinglan, Mao Jie
Department of Neurosurgery, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China.
Department of Neurosurgery, Yijishan Hospital, Wannan Medical College, Wuhu, Anhui, China.
Oncogenesis. 2020 Apr 14;9(4):39. doi: 10.1038/s41389-020-0223-2.
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.
增强的迁移能力对于胶质母细胞瘤（GBM）的恶性发展至关重要，但调节GBM细胞迁移的潜在分子机制仍不清楚。在这里，我们表明，与正常或低级别胶质瘤相比，核因子IX（NFIX）在人类GBM病变中显著上调。NFIX缺乏会损害GBM细胞的迁移，并抑制免疫缺陷裸鼠海马体中的肿瘤生长。从机制上讲，NFIX沉默会抑制埃兹蛋白（Ezrin）的表达，埃兹蛋白是一种将肌动蛋白细胞骨架与质膜交联的蛋白质，它也与GBM恶性程度呈正相关。补充埃兹蛋白可以挽救NFIX缺失诱导的GBM细胞迁移抑制。此外，我们在埃兹蛋白基因启动子区域-840至-825 bp之间鉴定出一个NFIX反应元件（RE）。总之，我们的研究结果首次表明，NFIX可以转录上调埃兹蛋白的表达，并促进GBM细胞迁移增强，这表明NFIX是GBM治疗的一个潜在靶点。
