title: miRNA signature of unfolded protein response in H9c2 rat cardiomyoblasts.
abstract: BACKGROUND
  Glucose and oxygen deprivation during ischemia is known to affect the homeostasis of the endoplasmic reticulum (ER) in ways predicted to activate the unfolded protein response (UPR). Activation of UPR signalling due to ER stress is associated with the development of myocardial infarction (MI). MicroRNAs (miRNAs) are key regulators of cardiovascular development and deregulation of miRNA expression is involved in the onset of many cardiovascular diseases. However, little is known about the mechanisms regulating the miRNA expression in the cardiovascular system during disease development and progression. Here we performed genome-wide miRNA expression profiling in rat cardiomyoblasts to identify the miRNAs deregulated during UPR, a crucial component of ischemia.
  
  
  RESULTS
  We found that expression of 86 microRNAs changed significantly during conditions of UPR in H9c2 cardiomyoblasts. We found that miRNAs with known function in cardiomyoblasts biology (miR-206, miR-24, miR-125b, miR-133b) were significantly deregulated during the conditions of UPR in H9c2 cells. The expression of miR-7a was upregulated by UPR and simulated in vitro ischemia in cardiomyoblasts. Further, ectopic expression of miR-7a provides resistance against UPR-mediated apoptosis in cardiomyoblasts. The ample overlap of miRNA expression signature between our analysis and different models of cardiac dysfunction further confirms the role of UPR in cardiovascular diseases.
  
  
  CONCLUSIONS
  This study demonstrates the role of UPR in deregulating the expression of miRNAs in MI. Our results provide novel insights about the molecular mechanisms of deregulated miRNA expression during the heart disease pathogenesis.
authors.affiliation: Discipline of Pathology, School of medicine, Clinical Science Institute, National University of Ireland Galway, Galway, Ireland.
authors.forename: Danielle E
authors.initials: DE
authors.lastname: Read
authors.affiliation: Discipline of Pathology, School of medicine, Clinical Science Institute, National University of Ireland Galway, Galway, Ireland.
authors.forename: Ananya
authors.initials: A
authors.lastname: Gupta
authors.affiliation: Center for Cardiovascular Research, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Yury
authors.initials: Y
authors.lastname: Ladilov
authors.affiliation: Apoptosis Research Centre, School of Natural Sciences, National University of Ireland Galway, Galway, Ireland.
authors.forename: Afshin
authors.initials: A
authors.lastname: Samali
authors.affiliation: Discipline of Pathology, School of medicine, Clinical Science Institute, National University of Ireland Galway, Galway, Ireland.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Gupta
keywords: Apoptosis; ER stress; MicroRNAs; Mir-7a; Myocardial infarction; Unfolded protein response