title: ROS-mediated bidirectional regulation of miRNA results in distinct pathologic heart conditions.
abstract: Under distinct pathological heart conditions, the expression of a single miRNA can display completely opposite patterns. However, the mechanism underlying the bidirectional regulation of a single miRNA and the clinical implications of this regulation remain largely unknown. To address this issue, we examined the regulation of miR-1, one of the most abundant miRNAs in the heart, during cardiac hypertrophy and ischemia/reperfusion (I/R). Our data indicated that different magnitudes and chronicities of ROS levels in cardiomyocytes resulted in differential expression of miR-1, subsequently altering the expression of myocardin. In animal models, the administration of a miR-1 mimic attenuated cardiac hypertrophy by suppressing the transverse aortic constriction-induced increase in myocardin expression, whereas the administration of anti-miR-1 ameliorated I/R-induced cardiac apoptosis and deterioration of heart function. Our findings indicated that a pathologic stimulus such as ROS can bidirectionally alter the expression of miRNA to contribute to the development of pathological conditions exhibiting distinct phenotypes and that the meticulous adjustment of the pathological miRNA levels is required to improve clinical outcomes.
authors.affiliation: Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung, South Korea; Catholic Kwandong University International St. Mary's Hospital, Incheon, South Korea.
authors.forename: Seahyoung
authors.initials: S
authors.lastname: Lee
authors.affiliation: Severance Integrative Research Institute for Cerebral and Cardiovascular Disease, Yonsei University Health System, Seoul, South Korea.
authors.forename: Soyeon
authors.initials: S
authors.lastname: Lim
authors.affiliation: Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, South Korea.
authors.forename: Onju
authors.initials: O
authors.lastname: Ham
authors.affiliation: Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, South Korea.
authors.forename: Se-Yeon
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Integrated Omics for Biomedical Sciences, Yonsei University, Seoul, South Korea.
authors.forename: Chang Yeon
authors.initials: CY
authors.lastname: Lee
authors.affiliation: Department of Integrated Omics for Biomedical Sciences, Yonsei University, Seoul, South Korea.
authors.forename: Jun-Hee
authors.initials: JH
authors.lastname: Park
authors.affiliation: Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, South Korea.
authors.forename: Jiyun
authors.initials: J
authors.lastname: Lee
authors.affiliation: Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, South Korea.
authors.forename: Hyang-Hee
authors.initials: HH
authors.lastname: Seo
authors.affiliation: Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, South Korea.
authors.forename: Ina
authors.initials: I
authors.lastname: Yun
authors.affiliation: Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, South Korea.
authors.forename: Sun M
authors.initials: SM
authors.lastname: Han
authors.affiliation: Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung, South Korea.
authors.forename: Min-Ji
authors.initials: MJ
authors.lastname: Cha
authors.affiliation: Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung, South Korea; Catholic Kwandong University International St. Mary's Hospital, Incheon, South Korea.
authors.forename: Eunhyun
authors.initials: E
authors.lastname: Choi
authors.affiliation: Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung, South Korea; Catholic Kwandong University International St. Mary's Hospital, Incheon, South Korea. Electronic address: kchwang@cku.ac.kr.
authors.forename: Ki-Chul
authors.initials: KC
authors.lastname: Hwang
mesh_terms: D000818:Animals; D017209:Apoptosis; D006332:Cardiomegaly / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000235:genetics; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D000099251:Myocardin
chemical_list: D035683:MicroRNAs; D009687:Nuclear Proteins; D017382:Reactive Oxygen Species; D015534:Trans-Activators; D000099251:Myocardin; C544547:MIRN1 microRNA, human
keywords: Heart; ROS; miRNA regulation