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dc.contributor.authorWang, K.
dc.contributor.authorLiu, F.
dc.contributor.authorZhou, L-Y.
dc.contributor.authorDing, S-L.
dc.contributor.authorLong, B.
dc.contributor.authorLiu, C-Y.
dc.contributor.authorSun, T.
dc.contributor.authorFan, Y-Y.
dc.contributor.authorSun, L.
dc.contributor.authorLi, P-F.
dc.date.accessioned2013-12-13T19:51:55Z
dc.date.available2013-12-13T19:51:55Z
dc.date.issued2013-07
dc.identifier.bibliographicCitationWang, K., Liu, F., Zhou, L. Y., Ding, S. L., Long, B., Liu, C. Y., Sun, T., Fan, Y. Y., Sun, L. and Li, P. F. miR-874 regulates myocardial necrosis by targeting caspase-8. Cell Death & Disease. 2013. 4. DOI: 10.1038/cddis.2013.233en_US
dc.identifier.issn2041-4889
dc.identifier.urihttp://hdl.handle.net/10027/10912
dc.descriptionCell Death and Disease is an open-access journal published by Nature Publishing Group. 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/. © 2013 by : Nature Publishing Group, Cell Death and Disease. The publication is available at http://www.nature.com/cddis/index.html. doi: 10.1038/cddis.2013.233en_US
dc.description.abstractCardiomyocyte 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 H2O2 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.en_US
dc.description.sponsorshipThis work was supported by National Natural Science Foundation of China (30871243, 31010103911, 81270160, 81000034) and NIH (1R01HL102202).en_US
dc.language.isoen_USen_US
dc.publisherNature Publishing Groupen_US
dc.subjectmyocardial necrosisen_US
dc.subjectmiR-874en_US
dc.subjectcaspase-8en_US
dc.titlemiR-874 regulates myocardial necrosis by targeting caspase-8en_US
dc.typeArticleen_US


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