XB-ART-55412
Glia
2018 May 01;665:987-998. doi: 10.1002/glia.23296.
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MicroRNA-31 is required for astrocyte specification.
Meares GP
,
Rajbhandari R
,
Gerigk M
,
Tien CL
,
Chang C
,
Fehling SC
,
Rowse A
,
Mulhern KC
,
Nair S
,
Gray GK
,
Berbari NF
,
Bredel M
,
Benveniste EN
,
Nozell SE
.
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Previously, we determined microRNA-31 (miR-31) is a noncoding tumor suppressive gene frequently deleted in glioblastoma (GBM); miR-31 suppresses tumor growth, in part, by limiting the activity of NF-κB. Herein, we expand our previous studies by characterizing the role of miR-31 during neural precursor cell (NPC) to astrocyte differentiation. We demonstrate that miR-31 expression and activity is suppressed in NPCs by stem cell factors such as Lin28, c-Myc, SOX2 and Oct4. However, during astrocytogenesis, miR-31 is induced by STAT3 and SMAD1/5/8, which mediate astrocyte differentiation. We determined miR-31 is required for terminal astrocyte differentiation, and that the loss of miR-31 impairs this process and/or prevents astrocyte maturation. We demonstrate that miR-31 promotes astrocyte development, in part, by reducing the levels of Lin28, a stem cell factor implicated in NPC renewal. These data suggest that miR-31 deletions may disrupt astrocyte development and/or homeostasis.
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???displayArticle.grants??? [+]
T32 NS048039 NINDS NIH HHS , R01 CA138517 NCI NIH HHS , R01 CA158534 NCI NIH HHS , R01 GM098566 NIGMS NIH HHS , R01 CA194414 NCI NIH HHS , P30 CA013148 NCI NIH HHS
Species referenced: Xenopus laevis
Genes referenced: bmp2 ezh2 lin28a myc pou5f3 smad1 sox2 stat3 stat3.2
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