| Hypoxia-inducible factor 1-α induces miR-210 in normoxic differentiating myoblasts. | |
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MedLine Citation:
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PMID: 23148210 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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MicroRNA-210 (miR-210) induction is a virtually constant feature of the hypoxic response in both normal and transformed cells, regulating several key aspects of cardiovascular diseases and cancer. We found that miR-210 was induced in normoxic myoblasts upon myogenic differentiation both in vitro and in vivo. miR-210 transcription was activated in an hypoxia-inducible factor 1-α (Hif1a)-dependent manner, and chromatin immunoprecipitation experiments show that Hif1a bound to the miR-210 promoter only in differentiated myotubes. Accordingly, luciferase reporter assays demonstrated the functional relevance of the Hif1a binding site for miR-210 promoter activation in differentiating myoblasts. To investigate the functional relevance of increased miR-210 levels in differentiated myofibers, we blocked miR-210 with complementary locked nucleic acid oligonucleotides (anti-miR-210). We found that C2C12 myoblast cell line differentiation was largely unaffected by anti-miR-210. Likewise, miR-210 inhibition did not affect skeletal muscle regeneration following cardiotoxin damage. However, we found that miR-210 blockade greatly increased myotube sensitivity to oxidative stress and mitochondrial dysfunction. In conclusion, miR-210 is induced in normoxic myofibers, playing a cytoprotective role. |
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Authors:
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Lucia Cicchillitti; Valeria Di Stefano; Eleonora Isaia; Luca Crimaldi; Pasquale Fasanaro; Valeria Ambrosino; Annalisa Antonini; Maurizio C Capogrossi; Carlo Gaetano; Giulia Piaggio; Fabio Martelli |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2012-11-12 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 287 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2012 Dec |
Date Detail:
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Created Date: 2012-12-31 Completed Date: 2013-03-25 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 44761-71 Citation Subset: IM |
Affiliation:
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IRCCS-Policlinico San Donato, 20097 Milan, Italy. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Base Sequence Cell Differentiation* Cell Line Hypoxia-Inducible Factor 1, alpha Subunit / genetics, metabolism* Male Mice MicroRNAs / genetics*, metabolism Molecular Sequence Data Myoblasts / cytology*, metabolism* Oxygen / metabolism* Promoter Regions, Genetic |
| Chemical | |
Reg. No./Substance:
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0/Hif1a protein, mouse; 0/Hypoxia-Inducible Factor 1, alpha Subunit; 0/MIRN210 microRNA, mouse; 0/MicroRNAs; 7782-44-7/Oxygen |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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