The miR-223/nuclear factor I-A axis regulates glial precursor proliferation and tumorigenesis in the CNS. Academic Article uri icon

Overview

abstract

  • Contemporary views of tumorigenesis regard its inception as a convergence of genetic mutation and developmental context. Glioma is 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 that it is a conserved proliferative mechanism across CNS development and tumorigenesis.

publication date

  • August 14, 2013

Research

keywords

  • Cell Proliferation
  • Cell Transformation, Neoplastic
  • Glioma
  • MicroRNAs
  • NFI Transcription Factors
  • Neoplastic Stem Cells

Identity

PubMed Central ID

  • PMC3742938

Scopus Document Identifier

  • 84881525787

Digital Object Identifier (DOI)

  • 10.1016/j.ccr.2012.04.012

PubMed ID

  • 23946414

Additional Document Info

volume

  • 33

issue

  • 33