Abstract
Neural stem cells (NSCs) are multipotent and undifferentiated cells with the potential to differentiate into neuronal lineages and gliocytes. NSCs have the ability to generate and regenerate the brain, indicating the possibility of cell-based therapies for neurological disorders. miR-124 has been demonstrated as a modulator in the survival, expansion, and differentiation of NSCs. However, the underlying molecular mechanisms of miR-124 in NSC development are still far from being understood. The expressions of miR-124, dishevelled binding antagonist of beta-catenin 1 (DACT1), ki-67, Nestin, β-tubulin III, glial fibrillary acidic protein (GFAP), β-catenin, cyclinD1, and glycogen synthase kinase-3β (GSK-3β) were examined by qRT-PCR or western blot. Bioinformatics and Dual-Luciferase reporter assay were used to identify the interaction between miR-124 and DACT1. MTS analysis was performed to measure the viability of NSCs. Enhanced expression of miR-124 and lowered expression of DACT1 were observed during a 14-day NSC differentiation period. DACT1 was verified as a direct target of miR-124. Moreover, overexpression of miR-124 promoted NSC proliferation and induced neuron-specific differentiation, presented as increased cell viability, higher neurosphere number, elevated ki-67, Nestin, β-tubulin III expressions, and decreased GFAP expression. Similarly, DACT1 downregulation facilitated proliferation and neuronal differentiation of NSCs. Furthermore, DACT1 overexpression impaired miR-124-induced proliferation and differentiation of NSCs. Additionally, miR-124 stimulated Wnt/β-catenin signaling via suppressing DACT1 expression. miR-124 promoted proliferation and induced NSC differentiation to neurons by activation of Wnt/β-catenin pathway via targeting DACT1, providing a potential target and aiding the development of cell-based therapies for neurological disorders.
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Abbreviations
- NSCs:
-
Neural stem cells
- DACT1:
-
Dishevelled binding antagonist of beta-catenin 1
- GFAP:
-
Glial fibrillary acidic protein
- GSK-3β:
-
Glycogen synthase kinase-3β
- MSCs:
-
Mesenchymal stem cells
- ESCs:
-
Embryonic stem cells
- ASCs:
-
Adult stem cells
- MiRNAs:
-
microRNAs
- NT-3:
-
Neurotrophin-3
- BDNF:
-
Brain-derived neurotrophic factor
- PTBP1:
-
PTB/hnRNP I
- PD:
-
Parkinson’s disease
- AD:
-
Alzheimer’s disease
- HD:
-
Huntington’s disease
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Acknowledgements
This work was funded by Henan Science and Technology International Cooperation Project (No. 162102410065).
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All animal experiments were approved by the Animal Care and Use Committee of the First Affiliated Hospital of Zhengzhou University in accordance with the National Institutes of Healthy guidelines for Animal Research.
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Jiao, S., Liu, Y., Yao, Y. et al. miR-124 promotes proliferation and neural differentiation of neural stem cells through targeting DACT1 and activating Wnt/β-catenin pathways. Mol Cell Biochem 449, 305–314 (2018). https://doi.org/10.1007/s11010-018-3367-z
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DOI: https://doi.org/10.1007/s11010-018-3367-z