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miR-29a Modulates Neuronal Differentiation through Targeting REST in Mesenchymal Stem Cells
OBJECTIVE: To investigate the modulation of microRNAs (miRNAs) upon the neuronal differentiation of mesenchymal stem cells (MSCs) through targeting RE-1 Silencing Factor (REST), a mature neuronal gene suppressor in neuronal and un-neuronal cells. METHODS: Rat bone marrow derived–MSCs were induced in...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4026383/ https://www.ncbi.nlm.nih.gov/pubmed/24841827 http://dx.doi.org/10.1371/journal.pone.0097684 |
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author | Duan, Ping Sun, Shiling Li, Bo Huang, Chuntian Xu, Yan Han, Xuefei Xing, Ying Yan, Wenhai |
author_facet | Duan, Ping Sun, Shiling Li, Bo Huang, Chuntian Xu, Yan Han, Xuefei Xing, Ying Yan, Wenhai |
author_sort | Duan, Ping |
collection | PubMed |
description | OBJECTIVE: To investigate the modulation of microRNAs (miRNAs) upon the neuronal differentiation of mesenchymal stem cells (MSCs) through targeting RE-1 Silencing Factor (REST), a mature neuronal gene suppressor in neuronal and un-neuronal cells. METHODS: Rat bone marrow derived–MSCs were induced into neuron-like cells (MSC-NCs) by DMSO and BHA in vitro. The expression of neuron specific enolase (NSE), microtubule-associated protein tau (Tau), REST and its target genes, including synaptosomal-associated protein 25 (SNAP25) and L1 cell adhesion molecular (L1CAM), were detected in MSCs and MSC-NCs. miRNA array analysis was conducted to screen for the upregulated miRNAs after neuronal differentiation. TargetScan was used to predict the relationship between these miRNAs and REST gene, and dual luciferase reporter assay was applied to validate it. Gain and loss of function experiments were used to study the role of miR-29a upon neuronal differentiation of MSCs. The knockdown of REST was conducted to show that miR-29a affected this process through targeting REST. RESULTS: MSCs were induced into neuron-like cells which presented neuronal cell shape and expressed NSE and Tau. The expression of REST declined and the expression of SNAP25 and L1CAM increased upon the neuronal differentiation of MSCs. Among 14 upregulated miRNAs, miR-29a was validated to target REST gene. During the neuronal differentiation of MSCs, miR-29a inhibition blocked the downregulation of REST, as well as the upregulation of SNAP25, L1CAM, NSE and Tau. REST knockdown rescued the effect of miR-29a inhibition on the expression of NSE and Tau. Meanwhile, miR-29a knockin significantly decreased the expression of REST and increased the expression of SNAP25 and L1CMA in MSCs, but did not significantly affect the expression of NSE and Tau. CONCLUSION: miR-29a regulates neurogenic markers through targeting REST in mesenchymal stem cells, which provides advances in neuronal differentiation research and stem cell therapy for neurodegenerative diseases. |
format | Online Article Text |
id | pubmed-4026383 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-40263832014-05-21 miR-29a Modulates Neuronal Differentiation through Targeting REST in Mesenchymal Stem Cells Duan, Ping Sun, Shiling Li, Bo Huang, Chuntian Xu, Yan Han, Xuefei Xing, Ying Yan, Wenhai PLoS One Research Article OBJECTIVE: To investigate the modulation of microRNAs (miRNAs) upon the neuronal differentiation of mesenchymal stem cells (MSCs) through targeting RE-1 Silencing Factor (REST), a mature neuronal gene suppressor in neuronal and un-neuronal cells. METHODS: Rat bone marrow derived–MSCs were induced into neuron-like cells (MSC-NCs) by DMSO and BHA in vitro. The expression of neuron specific enolase (NSE), microtubule-associated protein tau (Tau), REST and its target genes, including synaptosomal-associated protein 25 (SNAP25) and L1 cell adhesion molecular (L1CAM), were detected in MSCs and MSC-NCs. miRNA array analysis was conducted to screen for the upregulated miRNAs after neuronal differentiation. TargetScan was used to predict the relationship between these miRNAs and REST gene, and dual luciferase reporter assay was applied to validate it. Gain and loss of function experiments were used to study the role of miR-29a upon neuronal differentiation of MSCs. The knockdown of REST was conducted to show that miR-29a affected this process through targeting REST. RESULTS: MSCs were induced into neuron-like cells which presented neuronal cell shape and expressed NSE and Tau. The expression of REST declined and the expression of SNAP25 and L1CAM increased upon the neuronal differentiation of MSCs. Among 14 upregulated miRNAs, miR-29a was validated to target REST gene. During the neuronal differentiation of MSCs, miR-29a inhibition blocked the downregulation of REST, as well as the upregulation of SNAP25, L1CAM, NSE and Tau. REST knockdown rescued the effect of miR-29a inhibition on the expression of NSE and Tau. Meanwhile, miR-29a knockin significantly decreased the expression of REST and increased the expression of SNAP25 and L1CMA in MSCs, but did not significantly affect the expression of NSE and Tau. CONCLUSION: miR-29a regulates neurogenic markers through targeting REST in mesenchymal stem cells, which provides advances in neuronal differentiation research and stem cell therapy for neurodegenerative diseases. Public Library of Science 2014-05-19 /pmc/articles/PMC4026383/ /pubmed/24841827 http://dx.doi.org/10.1371/journal.pone.0097684 Text en © 2014 Duan et al http://creativecommons.org/licenses/by/4.0/ 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 properly credited. |
spellingShingle | Research Article Duan, Ping Sun, Shiling Li, Bo Huang, Chuntian Xu, Yan Han, Xuefei Xing, Ying Yan, Wenhai miR-29a Modulates Neuronal Differentiation through Targeting REST in Mesenchymal Stem Cells |
title | miR-29a Modulates Neuronal Differentiation through Targeting REST in Mesenchymal Stem Cells |
title_full | miR-29a Modulates Neuronal Differentiation through Targeting REST in Mesenchymal Stem Cells |
title_fullStr | miR-29a Modulates Neuronal Differentiation through Targeting REST in Mesenchymal Stem Cells |
title_full_unstemmed | miR-29a Modulates Neuronal Differentiation through Targeting REST in Mesenchymal Stem Cells |
title_short | miR-29a Modulates Neuronal Differentiation through Targeting REST in Mesenchymal Stem Cells |
title_sort | mir-29a modulates neuronal differentiation through targeting rest in mesenchymal stem cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4026383/ https://www.ncbi.nlm.nih.gov/pubmed/24841827 http://dx.doi.org/10.1371/journal.pone.0097684 |
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