Hypoxia-inducible factor 1-α induces miR-210 in normoxic differentiating myoblasts

Lucia Cicchillitti, Valeria Di Stefano, Eleonora Isaia, Luca Crimaldi, Pasquale Fasanaro, Valeria Ambrosino, Annalisa Antonini, Maurizio C. Capogrossi, Carlo Gaetano, Giulia Piaggio, Fabio Martelli

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)44761-44771
Number of pages11
JournalJournal of Biological Chemistry
Volume287
Issue number53
DOIs
Publication statusPublished - Dec 28 2012

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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    Cicchillitti, L., Di Stefano, V., Isaia, E., Crimaldi, L., Fasanaro, P., Ambrosino, V., Antonini, A., Capogrossi, M. C., Gaetano, C., Piaggio, G., & Martelli, F. (2012). Hypoxia-inducible factor 1-α induces miR-210 in normoxic differentiating myoblasts. Journal of Biological Chemistry, 287(53), 44761-44771. https://doi.org/10.1074/jbc.M112.421255