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miR-34a Regulates Mouse Neural Stem Cell Differentiation
BACKGROUND: MicroRNAs (miRNAs or miRs) participate in the regulation of several biological processes, including cell differentiation. Recently, miR-34a has been implicated in the differentiation of monocyte-derived dendritic cells, human erythroleukemia cells, and mouse embryonic stem cells. In addi...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153928/ https://www.ncbi.nlm.nih.gov/pubmed/21857907 http://dx.doi.org/10.1371/journal.pone.0021396 |
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author | Aranha, Márcia M. Santos, Daniela M. Solá, Susana Steer, Clifford J. Rodrigues, Cecília M. P. |
author_facet | Aranha, Márcia M. Santos, Daniela M. Solá, Susana Steer, Clifford J. Rodrigues, Cecília M. P. |
author_sort | Aranha, Márcia M. |
collection | PubMed |
description | BACKGROUND: MicroRNAs (miRNAs or miRs) participate in the regulation of several biological processes, including cell differentiation. Recently, miR-34a has been implicated in the differentiation of monocyte-derived dendritic cells, human erythroleukemia cells, and mouse embryonic stem cells. In addition, members of the miR-34 family have been identified as direct p53 targets. However, the function of miR-34a in the control of the differentiation program of specific neural cell types remains largely unknown. Here, we investigated the role of miR-34a in regulating mouse neural stem (NS) cell differentiation. METHODOLOGY/PRINCIPAL FINDINGS: miR-34a overexpression increased postmitotic neurons and neurite elongation of mouse NS cells, whereas anti-miR-34a had the opposite effect. SIRT1 was identified as a target of miR-34a, which may mediate the effect of miR-34a on neurite elongation. In addition, acetylation of p53 (Lys 379) and p53-DNA binding activity were increased and cell death unchanged after miR-34a overexpression, thus reinforcing the role of p53 during neural differentiation. Interestingly, in conditions where SIRT1 was activated by pharmacologic treatment with resveratrol, miR-34a promoted astrocytic differentiation, through a SIRT1-independent mechanism. CONCLUSIONS: Our results provide new insight into the molecular mechanisms by which miR-34a modulates neural differentiation, suggesting that miR-34a is required for proper neuronal differentiation, in part, by targeting SIRT1 and modulating p53 activity. |
format | Online Article Text |
id | pubmed-3153928 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-31539282011-08-19 miR-34a Regulates Mouse Neural Stem Cell Differentiation Aranha, Márcia M. Santos, Daniela M. Solá, Susana Steer, Clifford J. Rodrigues, Cecília M. P. PLoS One Research Article BACKGROUND: MicroRNAs (miRNAs or miRs) participate in the regulation of several biological processes, including cell differentiation. Recently, miR-34a has been implicated in the differentiation of monocyte-derived dendritic cells, human erythroleukemia cells, and mouse embryonic stem cells. In addition, members of the miR-34 family have been identified as direct p53 targets. However, the function of miR-34a in the control of the differentiation program of specific neural cell types remains largely unknown. Here, we investigated the role of miR-34a in regulating mouse neural stem (NS) cell differentiation. METHODOLOGY/PRINCIPAL FINDINGS: miR-34a overexpression increased postmitotic neurons and neurite elongation of mouse NS cells, whereas anti-miR-34a had the opposite effect. SIRT1 was identified as a target of miR-34a, which may mediate the effect of miR-34a on neurite elongation. In addition, acetylation of p53 (Lys 379) and p53-DNA binding activity were increased and cell death unchanged after miR-34a overexpression, thus reinforcing the role of p53 during neural differentiation. Interestingly, in conditions where SIRT1 was activated by pharmacologic treatment with resveratrol, miR-34a promoted astrocytic differentiation, through a SIRT1-independent mechanism. CONCLUSIONS: Our results provide new insight into the molecular mechanisms by which miR-34a modulates neural differentiation, suggesting that miR-34a is required for proper neuronal differentiation, in part, by targeting SIRT1 and modulating p53 activity. Public Library of Science 2011-08-03 /pmc/articles/PMC3153928/ /pubmed/21857907 http://dx.doi.org/10.1371/journal.pone.0021396 Text en Aranha 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 Aranha, Márcia M. Santos, Daniela M. Solá, Susana Steer, Clifford J. Rodrigues, Cecília M. P. miR-34a Regulates Mouse Neural Stem Cell Differentiation |
title | miR-34a Regulates Mouse Neural Stem Cell Differentiation |
title_full | miR-34a Regulates Mouse Neural Stem Cell Differentiation |
title_fullStr | miR-34a Regulates Mouse Neural Stem Cell Differentiation |
title_full_unstemmed | miR-34a Regulates Mouse Neural Stem Cell Differentiation |
title_short | miR-34a Regulates Mouse Neural Stem Cell Differentiation |
title_sort | mir-34a regulates mouse neural stem cell differentiation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153928/ https://www.ncbi.nlm.nih.gov/pubmed/21857907 http://dx.doi.org/10.1371/journal.pone.0021396 |
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