The miR-223/nuclear factor I-A axis regulates glial precursor proliferation and tumorigenesis in the CNS

Stacey M. Glasgow, Dylan Laug, Vita S. Brawley, Zhiyuan Zhang, Amanda Corder, Zheng Yin, Stephen T C Wong, Xiao Nan Li, Aaron E. Foster, Nabil Ahmed, Benjamin Deneen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Contemporary views of tumorigenesis regard its inception as a convergence of genetic mutation and developmental context. Gliomais the most common and deadly malignancy in the CNS; therefore, understanding how regulators of glial development contribute to its formation remains a key question. Previously we identified nuclear factor I-A (NFIA) as a key regulator of developmental gliogenesis, while miR-223 has been shown to repress NFIA expression in other systems. Using this relationship as a starting point, we found that miR-223 can suppress glial precursor proliferation via repression of NFIA during chick spinal cord development. This relationship is conserved in glioma, as miR-223 and NFIA expression is negatively correlated in human glioma tumors, and the miR-223/NFIA axis suppresses tumorigenesis in a human glioma cell line. Subsequent analysis of NFIA function revealed that it directly represses p21 and is required for tumorigenesis in a mouse neural stem cell model of glioma. These studies represent the first characterization of miR-223/NFIA axis function in glioma and demonstrate thatitis a conserved proliferative mechanism across CNS development and tumorigenesis.

Original languageEnglish (US)
Pages (from-to)13560-13568
Number of pages9
JournalJournal of Neuroscience
Volume33
Issue number33
DOIs
StatePublished - 2013

ASJC Scopus subject areas

  • Neuroscience(all)

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