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 language | English |
|---|---|
| Pages (from-to) | 44761-44771 |
| Number of pages | 11 |
| Journal | Journal of Biological Chemistry |
| Volume | 287 |
| Issue number | 53 |
| DOIs | |
| Publication status | Published - Dec 28 2012 |
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ASJC Scopus subject areas
- Biochemistry
- Cell Biology
- Molecular Biology
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Hypoxia-inducible factor 1-α induces miR-210 in normoxic differentiating myoblasts. / Cicchillitti, Lucia; Di Stefano, Valeria; Isaia, Eleonora; Crimaldi, Luca; Fasanaro, Pasquale; Ambrosino, Valeria; Antonini, Annalisa; Capogrossi, Maurizio C.; Gaetano, Carlo; Piaggio, Giulia; Martelli, Fabio.
In: Journal of Biological Chemistry, Vol. 287, No. 53, 28.12.2012, p. 44761-44771.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Hypoxia-inducible factor 1-α induces miR-210 in normoxic differentiating myoblasts
AU - Cicchillitti, Lucia
AU - Di Stefano, Valeria
AU - Isaia, Eleonora
AU - Crimaldi, Luca
AU - Fasanaro, Pasquale
AU - Ambrosino, Valeria
AU - Antonini, Annalisa
AU - Capogrossi, Maurizio C.
AU - Gaetano, Carlo
AU - Piaggio, Giulia
AU - Martelli, Fabio
PY - 2012/12/28
Y1 - 2012/12/28
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84871746640&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84871746640&partnerID=8YFLogxK
U2 - 10.1074/jbc.M112.421255
DO - 10.1074/jbc.M112.421255
M3 - Article
C2 - 23148210
AN - SCOPUS:84871746640
VL - 287
SP - 44761
EP - 44771
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 53
ER -