title: miRNA-940 reduction contributes to human Tetralogy of Fallot development.
abstract: Tetralogy of Fallot (TOF) is a complex congenital heart defect and the microRNAs regulation in TOF development is largely unknown. Herein, we explored the role of miRNAs in TOF. Among 75 dysregulated miRNAs identified from human heart tissues, miRNA-940 was the most down-regulated one. Interestingly, miRNA-940 was most highly expressed in normal human right ventricular out-flow tract comparing to other heart chambers. As TOF is caused by altered proliferation, migration and/or differentiation of the progenitor cells of the secondary heart field, we isolated Sca-1(+) human cardiomyocyte progenitor cells (hCMPC) for miRNA-940 function analysis. miRNA-940 reduction significantly promoted hCMPCs proliferation and inhibited hCMPCs migration. We found that JARID2 is an endogenous target regulated by miRNA-940. Functional analyses showed that JARID2 also affected hCMPCs proliferation and migration. Thus, decreased miRNA-940 affects the proliferation and migration of the progenitor cells of the secondary heart field by targeting JARID2 and potentially leads to TOF development.
authors.affiliation: Key Laboratory of Basic Research in Cardiology of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai, China; Institute of Medical Genetics, Tongji University, Shanghai, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Liang
authors.forename: Xinran
authors.initials: X
authors.lastname: Xu
authors.forename: Fangfei
authors.initials: F
authors.lastname: Deng
authors.forename: Jing
authors.initials: J
authors.lastname: Feng
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Pan
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.forename: Dasheng
authors.initials: D
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Xingqun
authors.initials: X
authors.lastname: Liang
authors.forename: Yunfu
authors.initials: Y
authors.lastname: Sun
authors.forename: Junjie
authors.initials: J
authors.lastname: Xiao
authors.forename: Yi-Han
authors.initials: YH
authors.lastname: Chen
mesh_terms: D053687:Adult Stem Cells / Q000502:physiology*; D017209:Apoptosis; D001483:Base Sequence; D001665:Binding Sites; D016022:Case-Control Studies; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D015536:Down-Regulation; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000502:physiology; D063151:Polycomb Repressive Complex 2 / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D013771:Tetralogy of Fallot / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D059467:Transcriptome
chemical_list: C547777:JARID2 protein, human; C000594732:MIRN940 microRNA, human; D035683:MicroRNAs; D063151:Polycomb Repressive Complex 2
keywords: Tetralogy of Fallot; human cardiomyocyte progenitor cell; microRNA