title: miR-134 Modulates the Proliferation of Human Cardiomyocyte Progenitor Cells by Targeting Meis2.
abstract: Cardiomyocyte progenitor cells play essential roles in early heart development, which requires highly controlled cellular organization. microRNAs (miRs) are involved in various cell behaviors by post-transcriptional regulation of target genes. However, the roles of miRNAs in human cardiomyocyte progenitor cells (hCMPCs) remain to be elucidated. Our previous study showed that miR-134 was significantly downregulated in heart tissue suffering from congenital heart disease, underlying the potential role of miR-134 in cardiogenesis. In the present work, we showed that the upregulation of miR-134 reduced the proliferation of hCMPCs, as determined by EdU assay and Ki-67 immunostaining, while the inhibition of miR-134 exhibited an opposite effect. Both up- and downregulation of miR-134 expression altered the transcriptional level of cell-cycle genes. We identified Meis2 as the target of miR-134 in the regulation of hCMPC proliferation through bioinformatic prediction, luciferase reporter assay and western blot. The over-expression of Meis2 mitigated the effect of miR-134 on hCMPC proliferation. Moreover, miR-134 did not change the degree of hCMPC differentiation into cardiomyocytes in our model, suggesting that miR-134 is not required in this process. These findings reveal an essential role for miR-134 in cardiomyocyte progenitor cell biology and provide new insights into the physiology and pathology of cardiogenesis.
authors.affiliation: Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. 111yufei_wu@tongji.edu.cn.|Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. 111yufei_wu@tongji.edu.cn.|Institute of Medical Genetics, Tongji University, Shanghai 200092, China. 111yufei_wu@tongji.edu.cn.|Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. 111yufei_wu@tongji.edu.cn.
authors.forename: Ya-Han
authors.initials: YH
authors.lastname: Wu
authors.affiliation: Department of Pediatrics, Tongji Hospital, Tongji University, Shanghai 200120, China. hongzhao_tj@sohu.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. zlxiao56@163.com.|Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. zlxiao56@163.com.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. youyou131205@hotmail.com.|Institute of Medical Genetics, Tongji University, Shanghai 200092, China. youyou131205@hotmail.com.|Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. youyou131205@hotmail.com.
authors.forename: Chun-Xia
authors.initials: CX
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. 111yufei_wu@tongji.edu.cn.|Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. 111yufei_wu@tongji.edu.cn.
authors.forename: Yu-Fei
authors.initials: YF
authors.lastname: Wu
authors.affiliation: Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. zlxiao56@163.com.|Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. zlxiao56@163.com.
authors.forename: Li-Xiao
authors.initials: LX
authors.lastname: Zhen
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.
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. gedongx@163.com.|Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. gedongx@163.com.|Institute of Medical Genetics, Tongji University, Shanghai 200092, China. gedongx@163.com.
authors.forename: Dong-Xia
authors.initials: DX
authors.lastname: Ge
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. lilincn1@163.com.|Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. lilincn1@163.com.|Institute of Medical Genetics, Tongji University, Shanghai 200092, China. lilincn1@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.affiliation: Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. yiliu@tongji.edu.cn.|Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. yiliu@tongji.edu.cn.|Institute of Medical Genetics, Tongji University, Shanghai 200092, China. yiliu@tongji.edu.cn.
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.|Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120, China.|Institute of Medical Genetics, Tongji University, Shanghai 200092, China.
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. 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: D049109:Cell Proliferation; D002478:Cells, Cultured; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D032386:Myoblasts, Cardiac / Q000378:metabolism* / Q000502:physiology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D018398:Homeodomain Proteins; C491172:MEIS2 protein, human; C569273:MIRN134 microRNA, human; D035683:MicroRNAs; D014157:Transcription Factors
keywords: Meis2; hCMPCs; miR-134; proliferation