title: MiR-25 protects cardiomyocytes against oxidative damage by targeting the mitochondrial calcium uniporter.
abstract: MicroRNAs (miRNAs) are a class of small non-coding RNAs, whose expression levels vary in different cell types and tissues. Emerging evidence indicates that tissue-specific and -enriched miRNAs are closely associated with cellular development and stress responses in their tissues. MiR-25 has been documented to be abundant in cardiomyocytes, but its function in the heart remains unknown. Here, we report that miR-25 can protect cardiomyocytes against oxidative damage by down-regulating mitochondrial calcium uniporter (MCU). MiR-25 was markedly elevated in response to oxidative stimulation in cardiomyocytes. Further overexpression of miR-25 protected cardiomyocytes against oxidative damage by inactivating the mitochondrial apoptosis pathway. MCU was identified as a potential target of miR-25 by bioinformatical analysis. MCU mRNA level was reversely correlated with miR-25 under the exposure of H2O2, and MCU protein level was largely decreased by miR-25 overexpression. The luciferase reporter assay confirmed that miR-25 bound directly to the 3' untranslated region (UTR) of MCU mRNA. MiR-25 significantly decreased H2O2-induced elevation of mitochondrial Ca2+ concentration, which is likely to be the result of decreased activity of MCU. We conclude that miR-25 targets MCU to protect cardiomyocytes against oxidative damages. This finding provides novel insights into the involvement of miRNAs in oxidative stress in cardiomyocytes.
authors.affiliation: Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. panlei_east@126.com.|Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. panlei_east@126.com.|Institute of Medical Genetics, Tongji University, Shanghai 200092, China. panlei_east@126.com.|Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. panlei_east@126.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Pan
authors.affiliation: Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. huangbijun56@126.com.|Institute of Medical Genetics, Tongji University, Shanghai 200092, China. huangbijun56@126.com.|Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. huangbijun56@126.com.
authors.forename: Bi-Jun
authors.initials: BJ
authors.lastname: Huang
authors.affiliation: Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. maxiue1989@126.com.|Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. maxiue1989@126.com.
authors.forename: Xiu-E
authors.initials: XE
authors.lastname: Ma
authors.affiliation: Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. wangshiyi840101@sina.com.|Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. wangshiyi840101@sina.com.
authors.forename: Shi-Yi
authors.initials: SY
authors.lastname: Wang
authors.affiliation: Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. afenger@126.com.|Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. afenger@126.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Feng
authors.affiliation: Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. lvfeihom@163.com.|Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. lvfeihom@163.com.
authors.forename: Fei
authors.initials: F
authors.lastname: Lv
authors.affiliation: Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. liuyuan_wy@163.com.|Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. liuyuan_wy@163.com.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. liuyuan_wy@163.com.|Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. liuyuan_wy@163.com.|Institute of Medical Genetics, Tongji University, Shanghai 200092, China. liuyuan_wy@163.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. lichangming@outlook.com.|Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. lichangming@outlook.com.
authors.forename: Chang-Ming
authors.initials: CM
authors.lastname: Li
authors.affiliation: Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. dandanliang_tj@hotmail.com.|Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. dandanliang_tj@hotmail.com.|Institute of Medical Genetics, Tongji University, Shanghai 200092, China. dandanliang_tj@hotmail.com.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Liang
authors.affiliation: Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. junli@tongji.edu.cn.|Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. junli@tongji.edu.cn.|Institute of Medical Genetics, Tongji University, Shanghai 200092, China. junli@tongji.edu.cn.|Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. junli@tongji.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. xuliang_east@126.com.|Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. xuliang_east@126.com.|Institute of Medical Genetics, Tongji University, Shanghai 200092, China. xuliang_east@126.com.
authors.forename: Liang
authors.initials: L
authors.lastname: Xu
authors.affiliation: Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. yihanchen@tongji.edu.cn.|Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. yihanchen@tongji.edu.cn.|Institute of Medical Genetics, Tongji University, Shanghai 200092, China. yihanchen@tongji.edu.cn.|Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. yihanchen@tongji.edu.cn.|Department of Pathology and Pathophysiology, Tongji University School of Medicine, Shanghai 200092, China. yihanchen@tongji.edu.cn.
authors.forename: Yi-Han
authors.initials: YH
authors.lastname: Chen
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D035683:MicroRNAs / Q000235:genetics*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats
chemical_list: D020413:3' Untranslated Regions; D015220:Calcium Channels; C000598929:MIRN25 microRNA, rat; D035683:MicroRNAs; D012333:RNA, Messenger; C034703:mitochondrial calcium uniporter