title: MiR-499-5p protects cardiomyocytes against ischaemic injury via anti-apoptosis by targeting PDCD4.
abstract: Recent studies have reported that miRNAs might play critical roles in acute myocardial infarction (AMI). The objective of this study is to investigate the role of miR-499-5p in AMI and its potential molecular mechanisms. The expression level of MiR-499-5p was remarkably decreased in the infarcted myocardial tissues and in the cultured neonatal rat cardiomyocytes induced by hypoxia. Overexpression or knockdown of miR-499-5p decreased or increased the apoptotic rates of cultured cardiomyocytes in vitro. In addition, ectopic overexpression of miR-499-5p in the rat AMI models with agomir reduced the myocardial infarct size through decreasing the cardiomyocytes apoptosis in the infarcted area of the rat hearts. PDCD4 (programmed cell death 4) was verified as a direct target of miR-499-5p by luciferase report assay, and ectopic overexpression or inhibition of miR-499-5p could inhibit or increase the PDCD4 expression at both the mRNA and protein levels. Furthermore, we found that ectopic overexpression of PDCD4 without miR-499-5p binding sites reversed miR-499-5p-mediated cardiomyocytes apoptosis. Together, these findings revealed the role of miR-499-5p in protecting the cardiomyocytes against apoptosis induced by AMI via its direct target PDCD4, which providing evidence for the miR-499-5p/PDCD4 pathway as a potential therapeutic target for patients with AMI.
authors.affiliation: Department of Emergency, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China.
authors.forename: Yingqing
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Emergency, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Emergency, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China.
authors.forename: Xueming
authors.initials: X
authors.lastname: Bao
authors.affiliation: Department of Emergency, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China.
authors.forename: Xifu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Emergency, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China.
authors.forename: Junhua
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Emergency, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China.
authors.forename: Xiongbin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Emergency, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China.
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Hong
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D015687:Cell Hypoxia; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000473:pathology; D004195:Disease Models, Animal; D055785:Gene Knockdown Techniques; D020287:In Situ Nick-End Labeling; D008297:Male; D035683:MicroRNAs / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D009203:Myocardial Infarction / Q000473:pathology*; D009206:Myocardium / Q000473:pathology*; D032383:Myocytes, Cardiac; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
chemical_list: D051017:Apoptosis Regulatory Proteins; C558425:MIRN499 microRNA, rat; D035683:MicroRNAs; C467042:Pdcd4 protein, rat; D012333:RNA, Messenger
keywords: Pathology Section; acute myocardial infarction; cardiomyocytes apoptosis; ischaemic injury; miR-499-5p; programmed cell death 4