title: MicroRNA-2861 regulates programmed necrosis in cardiomyocyte by impairing adenine nucleotide translocase 1 expression.
abstract: Necrosis is programmed and is one of the main forms of cell death in the pathological process in cardiac diseases. MicroRNAs (miRNAs) have emerged as key gene regulators in many diseases. However, how miRNAs contribute to programmed necrosis is poorly defined. Here we report that miR-2861 and adenine nucleotide translocase 1 (ANT1) constitute an axis that regulates necrotic cell death in the heart. Our results show that ANT1 inhibits H2O2-induced cardiomyocytes necrosis. ANT1 also antagonizes myocardial necrosis in a mouse ischemia/reperfusion (I/R) model. We further demonstrate that miR-2861 directly binds to the coding sequence of ANT1 and suppresses the expression of ANT1 mRNA and protein. MiR-2861 induces necrotic cell death. In contrast, knockdown of miR-2861 attenuates H2O2-induced necrosis in cardiomyocytes. Also, miR-2861 knockdown protects heart from I/R injury and necrotic cell death in vivo. MiR-2861 regulates necrosis and myocardial infarction through targeting ANT1. Collectively, these data identify miR-2861 and ANT1 as two novel regulators of cardiomyocyte necrosis and myocardial infarction, and suggest potential therapeutic targets in treatment of cardiac diseases.
authors.affiliation: Center for Developmental Cardiology, Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao 266021, China. Electronic address: wangk696@163.com.
authors.forename: Kun
authors.initials: K
authors.lastname: Wang
authors.affiliation: Laboratory of Molecular Medicine, Central Research Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Long
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.affiliation: Center for Developmental Cardiology, Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao 266021, China.
authors.forename: Cui-Yun
authors.initials: CY
authors.lastname: Liu
authors.affiliation: Center for Developmental Cardiology, Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao 266021, China.
authors.forename: Yan-Han
authors.initials: YH
authors.lastname: Dong
authors.affiliation: Center for Developmental Cardiology, Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao 266021, China.
authors.forename: Jin-Ning
authors.initials: JN
authors.lastname: Gao
authors.affiliation: Center for Developmental Cardiology, Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao 266021, China.
authors.forename: Lu-Yu
authors.initials: LY
authors.lastname: Zhou
authors.affiliation: Center for Developmental Cardiology, Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao 266021, China.
authors.forename: Chao-Qun
authors.initials: CQ
authors.lastname: Wang
authors.affiliation: Center for Developmental Cardiology, Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao 266021, China. Electronic address: peifengliqd@163.com.
authors.forename: Pei-Feng
authors.initials: PF
authors.lastname: Li
mesh_terms: D033741:Adenine Nucleotide Translocator 1 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015870:Gene Expression; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008297:Male; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000502:physiology*; D008929:Mitochondria, Heart / Q000378:metabolism; D017202:Myocardial Ischemia / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000502:physiology*; D009336:Necrosis; D034622:RNA Interference
chemical_list: D033741:Adenine Nucleotide Translocator 1; C000607173:MIRN2861 microRNA, mouse; D035683:MicroRNAs; D006861:Hydrogen Peroxide