Nuclear factor IX promotes glioblastoma development through transcriptional activation of Ezrin

Zhuohao Liu, Ruixiang Ge, Jiayi Zhou, Xinzhi Yang, Kenneth King yip Cheng, Jingli Tao, Dinglan Wu, Jie Mao

Research output: Journal article publicationJournal articleAcademic researchpeer-review

Abstract

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.

Original languageEnglish
Article number39
JournalOncogenesis
Volume9
Issue number4
DOIs
Publication statusPublished - 14 Apr 2020

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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