TY - JOUR
T1 - Nuclear factor IX promotes glioblastoma development through transcriptional activation of Ezrin
AU - Liu, Zhuohao
AU - Ge, Ruixiang
AU - Zhou, Jiayi
AU - Yang, Xinzhi
AU - Cheng, Kenneth King yip
AU - Tao, Jingli
AU - Wu, Dinglan
AU - Mao, Jie
PY - 2020/4/14
Y1 - 2020/4/14
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85083678979&partnerID=8YFLogxK
U2 - 10.1038/s41389-020-0223-2
DO - 10.1038/s41389-020-0223-2
M3 - Journal article
AN - SCOPUS:85083678979
SN - 2157-9024
VL - 9
JO - Oncogenesis
JF - Oncogenesis
IS - 4
M1 - 39
ER -
