title: MiR-28 inhibits cardiomyocyte survival through suppressing PDK1/Akt/mTOR signaling.
abstract: MicroRNAs play critical roles in regulating cell survival under multiple pathological conditions of heart diseases. Oxidative stress-induced apoptosis contributes greatly to heart ischemia-reperfusion injury. Herein, we describe a novel regulatory role of miR-28 on the survival of cardiomyocytes. We show that miR-28 was upregulated in cardiomyocytes treated with hydrogen peroxide (H2O2). MiR-28 gain of function sensitized cell apoptosis, whereas miR-28 loss of function partially rescued cell apoptosis induced by H2O2. Importantly, we observed a significant reduction in Akt/mammalian target of rapamycin (mTOR) signaling activity after miR-28 treatment. Luciferase activity assay and western blot analysis both revealed that, phosphoinositide-dependent kinase-1 (PDK1), which is critical for Akt activation, was directly and negatively modulated by miR-28. Our results therefore indicate that miR-28 regulates oxidative stress-induced cell apoptosis in heart muscle cells, which possibly involves a PDK1/Akt/mTOR-dependent mechanism. MIR-28 could serve as a critical therapeutic target to diminish oxidative stress-induced cell death in the heart.
authors.affiliation: Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China.
authors.forename: Rui-Yao
authors.initials: RY
authors.lastname: Zhu
authors.affiliation: Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China.
authors.forename: Di
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China.
authors.forename: Han-Dong
authors.initials: HD
authors.lastname: Zou
authors.affiliation: Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China.
authors.forename: Xiao-Shu
authors.initials: XS
authors.lastname: Zuo
authors.affiliation: Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China.
authors.forename: Qing-Shan
authors.initials: QS
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Hubei Key Laboratory of Cardiology, No. 99 Zhangzhidong Road, Wuchang District, Wuhan, 430060, Hubei Province, People's Republic of China. huanghe2031@163.com.
authors.forename: He
authors.initials: H
authors.lastname: Huang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001483:Base Sequence; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000633:toxicity; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C000723159:MIRN28 microRNA, mouse; D035683:MicroRNAs; C000631433:Pdk1 protein, mouse; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D006861:Hydrogen Peroxide; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases
keywords: Akt; Apoptosis; Heart; MicroRNA; mTOR