Journal
JOURNAL OF NEUROSCIENCE
Volume 36, Issue 5, Pages 1698-1710Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.1240-15.2016
Keywords
cuprizone; microarray; microRNA; oligodendrocyte progenitor cell; remyelination
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Funding
- University of Louisville [RR15576/GM103507, NS054708]
- Commonwealth of Kentucky Challenge for Excellence
- Kentucky Spinal Cord and Head Injury Research Trust
- Norton Healthcare
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Oligodendrocyte (OL) loss contributes to the functional deficits underlying diseases with a demyelinating component. Remyelination by oligodendrocyte progenitor cells (OPCs) can restore these deficits. To understand the role that microRNAs (miRNAs) play in remyelination, 2',3'-cyclic-nucleotide 3'-phosphodiesterase-EGFP(+) mice were treated with cuprizone, and OPCs were sorted from the corpus callosum. Microarray analysis revealed that Sfmbt2 family miRNAs decreased during cuprizone treatment. One particular Sfmbt2 miRNA, miR-297c-5p, increased during mouse OPC differentiation in vitro and during callosal development in vivo. When overexpressed in both mouse embryonic fibroblasts and rat OPCs (rOPCs), cell cycle analysis revealed that miR-297c-5p promoted G(1)/G(0) arrest. Additionally, miR-297c-5p transduction increased the number of O1 (+) rOPCs during differentiation. Luciferase reporter assays confirmed that miR-297c-5p targets cyclin T2 (CCNT2), the regulatory subunit of positive transcription elongation factor b, a complex that inhibits OL maturation. Furthermore, CCNT2-specific knockdown promoted rOPC differentiation while not affecting cell cycle status. Together, these data support a dual role for miR-297c-5p as both a negative regulator of OPC proliferation and a positive regulator of OL maturation via its interaction with CCNT2.
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