The miR-223/nuclear factor I-A axis regulates glial precursor proliferation and tumorigenesis in the CNS.
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.
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas 77030, USA.
Stacey M
SM
Glasgow
Dylan
D
Laug
Vita S
VS
Brawley
Zhiyuan
Z
Zhang
Amanda
A
Corder
Zheng
Z
Yin
Stephen T C
ST
Wong
Xiao-Nan
XN
Li
Aaron E
AE
Foster
Nabil
N
Ahmed
Benjamin
B
Deneen
D000818:Animals; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D002642:Chick Embryo; D047369:Chromatin Immunoprecipitation; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D051839:NFI Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046888:Tissue Array Analysis; D023041:Xenograft Model Antitumor Assays
D035683:MicroRNAs; D051839:NFI Transcription Factors; C525067:MIR223, human