RT Journal Article
SR Electronic
T1 The miR-223/Nuclear Factor I-A Axis Regulates Glial Precursor Proliferation and Tumorigenesis in the CNS
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 13560
OP 13568
DO 10.1523/JNEUROSCI.0321-13.2013
VO 33
IS 33
A1 Stacey M. Glasgow
A1 Dylan Laug
A1 Vita S. Brawley
A1 Zhiyuan Zhang
A1 Amanda Corder
A1 Zheng Yin
A1 Stephen T. C. Wong
A1 Xiao-Nan Li
A1 Aaron E. Foster
A1 Nabil Ahmed
A1 Benjamin Deneen
YR 2013
UL http://www.jneurosci.org/content/33/33/13560.abstract
AB 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.