Research Papers:
MicroRNA-214 protects against hypoxia/reoxygenation induced cell damage and myocardial ischemia/reperfusion injury via suppression of PTEN and Bim1 expression
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Abstract
Xiaohui Wang1, Tuanzhu Ha1,4, Yuanping Hu1, Chen Lu1, Li Liu2, Xia Zhang1, Race Kao1,4, John Kalbfleisch3,4, David Williams1,4, Chuanfu Li1,4
1Department of Surgery, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA
2Department of Geriatrics, First Affiliated Hospital with Nanjing Medical University, Nanjing, China
3Department of Biometry and Medical Computing, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA
4Center of Excellence for Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA
Correspondence to:
Chuanfu Li, email: [email protected]
Keywords: microRNA-214, myocardial ischemia/reperfusion injury, myocardial apoptosis, PTEN, Bim1
Received: September 24, 2016 Accepted: October 28, 2016 Published: November 22, 2016
ABSTRACT
Background: Myocardial apoptosis plays an important role in myocardial ischemia/reperfusion (I/R) injury. Activation of PI3K/Akt signaling protects the myocardium from I/R injury. This study investigated the role of miR-214 in hypoxia/reoxygenation (H/R)-induced cell damage in vitro and myocardial I/R injury in vivo.
Methods and Results: H9C2 cardiomyoblasts were transfected with lentivirus expressing miR-214 (LmiR-214) or lentivirus expressing scrambled miR-control (LmiR-control) respectively, to establish cell lines of LmiR-214 and LmiR-control. The cells were subjected to hypoxia for 4 h followed by reoxygenation for 24 h. Transfection of LmiR-214 suppresses PTEN expression, significantly increases the levels of Akt phosphorylation, markedly attenuates LDH release, and enhances the viability of the cells subjected to H/R. In vivo transfection of mouse hearts with LmiR-214 significantly attenuates I/R induced cardiac dysfunction and reduces I/R-induced myocardial infarct size. LmiR-214 transfection significantly attenuates I/R-induced myocardial apoptosis and caspase-3/7 and caspase-8 activity. Increased expression of miR-214 by transfection of LmiR-214 suppresses PTEN expression, increases the levels of phosphorylated Akt, represses Bim1 expression and induces Bad phosphorylation in the myocardium. In addition, in vitro data shows transfection of miR-214 mimics to H9C2 cells suppresses the expression and translocation of Bim1 from cytosol to mitochondria and induces Bad phosphorylation.
Conclusions: Our in vitro and in vivo data suggests that miR-214 protects cells from H/R induced damage and attenuates I/R induced myocardial injury. The mechanisms involve activation of PI3K/Akt signaling by targeting PTEN expression, induction of Bad phosphorylation, and suppression of Bim1 expression, resulting in decreases in I/R-induced myocardial apoptosis.
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