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

SM Glasgow, D Laug, VS Brawley, Z Zhang… - Journal of …, 2013 - Soc Neuroscience
SM Glasgow, D Laug, VS Brawley, Z Zhang, A Corder, Z Yin, STC Wong, XN Li, AE Foster
Journal of Neuroscience, 2013Soc Neuroscience
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 IA (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 …
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.
Soc Neuroscience