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. Wong, Xiao Nan Li, Aaron E. Foster, Nabil Ahmed, Benjamin Deneen

Research output: Contribution to journalArticle

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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