Open AccessArticle
miR-134 Modulates the Proliferation of Human Cardiomyocyte Progenitor Cells by Targeting Meis2
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Ya-Han Wu 1,2,3,4,†, Hong Zhao 5,†, Li-Ping Zhou 1,4,†, Chun-Xia Zhao 1,3,4,†, Yu-Fei Wu 1,4, Li-Xiao Zhen 1,4, Jun Li 1,2,3, Dong-Xia Ge 1,2,3, Liang Xu 1,2,3, Li Lin 1,2,3, Yi Liu 1,2,3, Dan-Dan Liang 1,2,3 and Yi-Han Chen 1,2,3,4,6,*
1
Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, China
2
Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120, China
3
Institute of Medical Genetics, Tongji University, Shanghai 200092, China
4
Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China
5
Department of Pediatrics, Tongji Hospital, Tongji University, Shanghai 200120, China
6
Department of Pathology and Pathophysiology, Tongji University School of Medicine, Shanghai 200092, China
†
These authors contributed equally to this work.
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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
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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.
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