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miR-874 regulates myocardial necrosis by targeting caspase-8
Cardiomyocyte death is an important reason for the cardiac syndromes, such as heart failure (HF) and myocardial infarction (MI). In the heart diseases, necrosis is one of the main forms of cell death. MicroRNAs (miRNAs) are a class of small non-coding RNAs that mediate post-transcriptional gene sile...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3730407/ https://www.ncbi.nlm.nih.gov/pubmed/23828572 http://dx.doi.org/10.1038/cddis.2013.233 |
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author | Wang, K Liu, F Zhou, L-Y Ding, S-L Long, B Liu, C-Y Sun, T Fan, Y-Y Sun, L Li, P-F |
author_facet | Wang, K Liu, F Zhou, L-Y Ding, S-L Long, B Liu, C-Y Sun, T Fan, Y-Y Sun, L Li, P-F |
author_sort | Wang, K |
collection | PubMed |
description | Cardiomyocyte death is an important reason for the cardiac syndromes, such as heart failure (HF) and myocardial infarction (MI). In the heart diseases, necrosis is one of the main forms of cell death. MicroRNAs (miRNAs) are a class of small non-coding RNAs that mediate post-transcriptional gene silencing. Hitherto, it is not yet clear whether miRNA can regulate necrosis in cardiomyocyte. In this work, we performed a microarray to detect miRNAs in response to H(2)O(2) treatment, and the results showed that miR-874 was substantially increased. We further studied the function of miR-874, and observed that knockdown of miR-874 attenuated necrosis in the cellular model and also MI in the animal model. We searched for the downstream mediator of miR-874 and identified that caspase-8 was a target of miR-874. Caspase-8 was able to antagonize necrosis. When suppressed by miR-874, caspase-8 lost the ability to repress necrotic program. In exploring the molecular mechanism by which miR-874 expression is regulated, we identified that Foxo3a could transcriptionally repress miR-874 expression. Foxo3a transgenic or knockout mice exhibited a low or high expression level of miR-874, and a reduced or enhanced necrosis and MI. Our present study reveals a novel myocardial necrotic regulating model, which is composed of Foxo3a, miR-874 and caspase-8. Modulation of their levels may provide a new approach for tackling myocardial necrosis. |
format | Online Article Text |
id | pubmed-3730407 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-37304072013-08-01 miR-874 regulates myocardial necrosis by targeting caspase-8 Wang, K Liu, F Zhou, L-Y Ding, S-L Long, B Liu, C-Y Sun, T Fan, Y-Y Sun, L Li, P-F Cell Death Dis Original Article Cardiomyocyte death is an important reason for the cardiac syndromes, such as heart failure (HF) and myocardial infarction (MI). In the heart diseases, necrosis is one of the main forms of cell death. MicroRNAs (miRNAs) are a class of small non-coding RNAs that mediate post-transcriptional gene silencing. Hitherto, it is not yet clear whether miRNA can regulate necrosis in cardiomyocyte. In this work, we performed a microarray to detect miRNAs in response to H(2)O(2) treatment, and the results showed that miR-874 was substantially increased. We further studied the function of miR-874, and observed that knockdown of miR-874 attenuated necrosis in the cellular model and also MI in the animal model. We searched for the downstream mediator of miR-874 and identified that caspase-8 was a target of miR-874. Caspase-8 was able to antagonize necrosis. When suppressed by miR-874, caspase-8 lost the ability to repress necrotic program. In exploring the molecular mechanism by which miR-874 expression is regulated, we identified that Foxo3a could transcriptionally repress miR-874 expression. Foxo3a transgenic or knockout mice exhibited a low or high expression level of miR-874, and a reduced or enhanced necrosis and MI. Our present study reveals a novel myocardial necrotic regulating model, which is composed of Foxo3a, miR-874 and caspase-8. Modulation of their levels may provide a new approach for tackling myocardial necrosis. Nature Publishing Group 2013-07 2013-07-04 /pmc/articles/PMC3730407/ /pubmed/23828572 http://dx.doi.org/10.1038/cddis.2013.233 Text en Copyright © 2013 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/ |
spellingShingle | Original Article Wang, K Liu, F Zhou, L-Y Ding, S-L Long, B Liu, C-Y Sun, T Fan, Y-Y Sun, L Li, P-F miR-874 regulates myocardial necrosis by targeting caspase-8 |
title | miR-874 regulates myocardial necrosis by targeting caspase-8 |
title_full | miR-874 regulates myocardial necrosis by targeting caspase-8 |
title_fullStr | miR-874 regulates myocardial necrosis by targeting caspase-8 |
title_full_unstemmed | miR-874 regulates myocardial necrosis by targeting caspase-8 |
title_short | miR-874 regulates myocardial necrosis by targeting caspase-8 |
title_sort | mir-874 regulates myocardial necrosis by targeting caspase-8 |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3730407/ https://www.ncbi.nlm.nih.gov/pubmed/23828572 http://dx.doi.org/10.1038/cddis.2013.233 |
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