Document Detail


Hypoxia-inducible factor 1-α induces miR-210 in normoxic differentiating myoblasts.
MedLine Citation:
PMID:  23148210     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-11-12
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  287     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-31     Completed Date:  2013-03-25     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  44761-71     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
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:
0/Hif1a protein, mouse; 0/Hypoxia-Inducible Factor 1, alpha Subunit; 0/MIRN210 microRNA, mouse; 0/MicroRNAs; S88TT14065/Oxygen
Comments/Corrections

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