MicroRNA-125b protects against myocardial ischaemia/reperfusion injury via targeting p53-mediated apoptotic signalling and TRAF6

Cardiovasc Res. 2014 Jun 1;102(3):385-95. doi: 10.1093/cvr/cvu044. Epub 2014 Feb 27.


Aims: The present study examined the role of microRNA-125b (miR-125b) in myocardial ischaemia/reperfusion (I/R) injury. We constructed lentivirus-expressing miR-125b (LmiR-125b) and developed transgenic mice with overexpression of miR-125b.

Methods and results: LmiR-125b was transfected into mouse hearts through the right common carotid artery. Lentivirus vector (LmiR-Con) served as vector control. Untreated mice served as I/R control. Sham operation served as sham control. Seven days after transfection, the hearts were subjected to ischaemia (45 min) followed by reperfusion (4 h). Myocardial infarct size was analysed by 2,3,5-triphenyltetrazolium chloride staining. In separate experiments, hearts were subjected to ischaemia (45 min) followed by reperfusion for up to 7 days. Cardiac function was measured by echocardiography before, as well as 3 and 7 days after myocardial I/R. Increased expression of miR-125b significantly decreased I/R-induced myocardial infarct size by 60% and prevented I/R-induced decreases in ejection fraction (EF%) and fractional shortening (%FS). Transgenic mice with overexpression of miR-125b also showed the protection against myocardial I/R injury. Increased expression of miR-125b attenuated I/R-induced myocardial apoptosis and caspase-3/7 and -8 activities. Western blot showed that increased expression of miR-125b suppresses p53 and Bak1 expression in the myocardium. In addition, transfection of LmiR-125b decreased the levels of TNF receptor-associated factor 6 (TRAF6) and prevented I/R-induced NF-κB activation.

Conclusion: miR-125 protects the myocardium from I/R injury by preventing p53-mediated apoptotic signalling and suppressing TRAF6-mediated NF-κB activation.

Keywords: Apoptosis; MicroRNA-125b; Myocardial I/R; NF-κB; p53.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apoptosis*
  • Caspases / physiology
  • Cells, Cultured
  • Lentivirus / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / physiology*
  • Myocardial Infarction / pathology
  • Myocardial Reperfusion Injury / prevention & control*
  • Myocardium / pathology*
  • Myocytes, Cardiac / metabolism
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / physiology
  • Neutrophil Infiltration
  • Rats
  • Signal Transduction / physiology*
  • TNF Receptor-Associated Factor 6 / physiology*
  • Tumor Suppressor Protein p53 / physiology*
  • bcl-2 Homologous Antagonist-Killer Protein / analysis


  • Bak1 protein, mouse
  • MicroRNAs
  • Mirn125 microRNA, mouse
  • NF-kappa B
  • TNF Receptor-Associated Factor 6
  • Tumor Suppressor Protein p53
  • bcl-2 Homologous Antagonist-Killer Protein
  • Caspases