miR-21 Functions Oppositely in Proliferation and Differentiation of Neural
Stem/Precursor Cells via Regulating AKT and GSK-3ÃÂ²
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Received Date: Nov 30, -0001 / Accepted Date: Nov 30, -0001 /
Published Date: Dec 13, 2016
Copyright: © 2016 . This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
MicroRNA involves in regulating behavior of neural stem/precursor cells (NSPCs), thus it offers the potential to treat central nervous system disease. However, the effect of miR-21 on NSPCs remains unknown. In this study, we demonstrated that miR-21 reduced proliferation and promoted neural differentiation in NSPCs via regulating the activation of AKT and GSK-3β signaling pathways in vitro. During differentiation of NSPCs, the expression of miR-21 was increased in a time-dependent manner by qRT-PCR. Synthesized pre-miR-21 or anti-miR-21 was transfected into NSPCs, thereby efficiently over-expressing or knocking down miR-21. Overexpression of miR-21 promoted the neural differentiation of NSPCs, as indicated by Tuj1 and PSA-NCAM staining. Interestingly, knocking down miR-21 had the opposite effect of neural differentiation in NSPCs. However, in proliferation area, overexpression of miR-21 decreased the cell viability by 3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine hydrochloride (MTT) assay, and inhibited the proliferation of NSPCs, as indicated by 5-Bromo-2-deoxyUridine (BrdU) staining. And likewise, knocking down miR-21 had the opposite effect of cell viability and proliferation. Western blot showed that overexpression of miR-21 enhanced the expression of Cyclin D1; however, knocking down miR-21 prevented its expression. Furthermore, we revealed that protein kinase B (AKT) and glycogen synthase kinase-3 beta (GSK-3β) signaling pathways were involved in the proliferation and neural differentiation of NSPCs. Overexpression of miR-21 activated AKT, and the p-GSK-3β was increased. Conversely, knocking down miR-21 blocked the activation of AKT, and decreased the phosphorylation level of GSK-3β. These results demonstrated that miR-21 promotes neural differentiation and reduces proliferation in NSPCs via regulating AKT and GSK-3β pathways. These findings may help to develop strategies for treatment of central nervous system diseases.