title: Down-regulation of microRNA-451a facilitates the activation and proliferation of CD4+T cells by targeting Myc in patients with dilated cardiomyopathy.
abstract: CD4+T cells are abnormally activated in patients with dilated cardiomyopathy (DCM) and might be associated with the immunopathogenesis of the disease. However, the underlying mechanisms of CD4+T cell activation remain largely undefined. Our aim was to investigate whether the dysregulation of microRNAs (miRNAs) was associated with CD4+T cell activation in DCM. CD4+T cells from DCM patients showed increased expression levels of CD25 and CD69 and enhanced proliferation in response to anti-CD3/28, indicating an activated state. miRNA profiling analysis of magnetically sorted CD4+T cells revealed a distinct pattern of miRNA expression in CD4+T cells from DCM patients compared with controls. The level of miRNA-451a (miR-451a) was significantly decreased in the CD4+T cells of DCM patients compared with that of the controls. The transfection of T cells with an miR-451a mimic inhibited their activation and proliferation, whereas an miR-451a inhibitor produced the opposite effects. Myc was directly inhibited by miR-451a via interaction with its 3'-UTR, thus identifying it as an miR-451a target in T cells. The knockdown of Myc suppressed the activation and proliferation of T cells, and the expression of Myc was significantly up-regulated at the mRNA level in CD4+T cells from patients with DCM. A strong inverse correlation was observed between the Myc mRNA expression and miR-451a transcription level. Our data suggest that the down-regulation of miR-451a contributes to the activation and proliferation of CD4+T cells by targeting the transcription factor Myc in DCM patients and may contribute to the immunopathogenesis of DCM.
authors.affiliation: From the Laboratory of Cardiovascular Immunology, Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, 430022 Wuhan and.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: From the Laboratory of Cardiovascular Immunology, Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, 430022 Wuhan and.
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.affiliation: From the Laboratory of Cardiovascular Immunology, Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, 430022 Wuhan and.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: From the Laboratory of Cardiovascular Immunology, Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, 430022 Wuhan and.
authors.forename: Ni
authors.initials: N
authors.lastname: Xia
authors.affiliation: From the Laboratory of Cardiovascular Immunology, Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, 430022 Wuhan and.
authors.forename: Shaofang
authors.initials: S
authors.lastname: Nie
authors.affiliation: From the Laboratory of Cardiovascular Immunology, Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, 430022 Wuhan and.
authors.forename: Bingjie
authors.initials: B
authors.lastname: Lv
authors.affiliation: From the Laboratory of Cardiovascular Immunology, Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, 430022 Wuhan and.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: the Key Laboratory of Molecular Biophysics of the Ministry of Education, Cardio-X Center, College of Life Science and Technology and Center for Human Genome Research, Huazhong University of Science and Technology, 430074 Wuhan, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Tu
authors.affiliation: the Key Laboratory of Molecular Biophysics of the Ministry of Education, Cardio-X Center, College of Life Science and Technology and Center for Human Genome Research, Huazhong University of Science and Technology, 430074 Wuhan, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Li
authors.affiliation: From the Laboratory of Cardiovascular Immunology, Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, 430022 Wuhan and tangtingting@hust.edu.cn.
authors.forename: Tingting
authors.initials: T
authors.lastname: Tang
authors.affiliation: From the Laboratory of Cardiovascular Immunology, Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, 430022 Wuhan and nathancx@hust.edu.cn.
authors.forename: Xiang
authors.initials: X
authors.lastname: Cheng
mesh_terms: D020121:5' Untranslated Regions / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002311:Cardiomyopathy, Dilated / Q000276:immunology* / Q000473:pathology; D049109:Cell Proliferation; D015536:Down-Regulation / Q000276:immunology*; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D035683:MicroRNAs / Q000276:immunology*; D016271:Proto-Oncogene Proteins c-myc / Q000276:immunology*
chemical_list: D020121:5' Untranslated Regions; D015703:Antigens, CD; C531201:MIRN451 microRNA, human; C489427:MYC protein, human; D035683:MicroRNAs; D016271:Proto-Oncogene Proteins c-myc
keywords: Myc (c-Myc); T helper cells; cardiovascular disease; inflammation; microRNA (miRNA)