title: miR-22 regulates starvation-induced autophagy and apoptosis in cardiomyocytes by targeting p38α.
abstract: microRNAs (miRNAs) are short noncoding RNAs that function in RNA silencing and post-transcriptional regulation of gene expression. They play critical regulatory roles in many cardiovascular diseases, including ischemia-induced cardiac injury. Here, we report microRNA-22, highly expressed in the heart, can protect cardiomyocytes from starvation-induced injury through promoting autophagy and inhibiting apoptosis. Quantitative real-time PCR (qPCR) demonstrated that the expression of miR-22 in starvation-treated neonatal rat cardiomyocytes (NRCMs) was markedly down-regulated. Over-expression of miR-22 significantly promoted starvation-induced autophagy and inhibited starvation-induced apoptosis in NRCMs. In contrast, reduction of miR-22 suppressed autophagy and accelerated apoptosis in starving NRCMs. Immunohistochemistry and TUNEL staining results also provided further evidence that miR-22 promoted autophagy and inhibited apoptosis in myocardial cells. Furthermore, both luciferase reporter assay and western blot analysis were performed to identify p38α as a direct target of miR-22. Taken together, miR-22 plays an important role in regulating autophagy and apoptosis in ischemic myocardium through targeting p38α. miR-22 may represent a potential therapeutic target for the treatment of ischemic heart diseases.
authors.affiliation: Department of Cardiology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Guoran
authors.initials: G
authors.lastname: Li
authors.affiliation: Institution of Thoracic Cardiac Surgery, Department of Cardiothoracic Surgery, Changhai Hospital, Shanghai 200433, China.
authors.forename: Guokun
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Liangliang
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Cardiology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Cardiology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Jingwen
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Cardiology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China. Electronic address: mlp-125@163.com.
authors.forename: Liping
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Cardiology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China. Electronic address: xianxianz2010@163.com.
authors.forename: Xianxian
authors.initials: X
authors.lastname: Zhao
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D001343:Autophagy; D001483:Base Sequence; D019610:Cytoprotection; D005786:Gene Expression Regulation; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: C580892:MIRN22 microRNA, rat; D035683:MicroRNAs; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Apoptosis; Autophagy; Cardiomyocytes; Myocardial infarction; microRNAs; p38α