title: Integrated mRNA-microRNA profiling of human NK cell differentiation identifies MiR-583 as a negative regulator of IL2Rγ expression.
abstract: Natural killer (NK) cells are innate immune effector cells that protect against cancer and some viral infections. Until recently, most studies have investigated the molecular signatures of human or mouse NK cells to identify genes that are specifically expressed during NK cell development. However, the mechanism regulating NK cell development remains unclear. Here, we report a regulatory network of potential interactions during in vitro differentiation of human NK cells, identified using genome-wide mRNA and miRNA databases through hierarchical clustering analysis, gene ontology analysis and a miRNA target prediction program. The microRNA (miR)-583, which demonstrated the largest ratio change in mature NK cells, was highly correlated with IL2 receptor gamma (IL2Rγ) expression. The overexpression of miR-583 had an inhibitory effect on NK cell differentiation. In a reporter assay, the suppressive effect of miR-583 was ablated by mutating the putative miR-583 binding site of the IL2Rγ 3' UTR. Therefore, we show that miR-583 acts as a negative regulator of NK cell differentiation by silencing IL2Rγ. Additionally, we provide a comprehensive database of genome-wide mRNA and miRNA expression during human NK cell differentiation, offering a better understanding of basic human NK cell biology for the application of human NK cells in immunotherapy.
authors.affiliation: Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
authors.forename: Sohyun
authors.initials: S
authors.lastname: Yun
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Ochang-eup, Republic of Korea.
authors.forename: Su Ui
authors.initials: SU
authors.lastname: Lee
authors.affiliation: NAR Center, Inc., Daejeon Oriental Hospital of Daejeon University, Daejeon, Republic of Korea.
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Ochang-eup, Republic of Korea.
authors.forename: Hyun-Jun
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Song
authors.affiliation: Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
authors.forename: Young Kyeung
authors.initials: YK
authors.lastname: Kim
authors.affiliation: Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
authors.forename: Haiyoung
authors.initials: H
authors.lastname: Jung
authors.affiliation: Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
authors.forename: Young-Jun
authors.initials: YJ
authors.lastname: Park
authors.affiliation: Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
authors.forename: Suk Ran
authors.initials: SR
authors.lastname: Yoon
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Ochang-eup, Republic of Korea.
authors.forename: Sei-Ryang
authors.initials: SR
authors.lastname: Oh
authors.affiliation: Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea; Department of Functional Genomics, Korea University of Science and Technology, Daejeon, Republic of Korea.
authors.forename: Tae-Don
authors.initials: TD
authors.lastname: Kim
authors.affiliation: Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea; Department of Functional Genomics, Korea University of Science and Technology, Daejeon, Republic of Korea.
authors.forename: Inpyo
authors.initials: I
authors.lastname: Choi
mesh_terms: D020413:3' Untranslated Regions; D001483:Base Sequence; D001665:Binding Sites; D002454:Cell Differentiation; D002478:Cells, Cultured; D016000:Cluster Analysis; D030541:Databases, Genetic; D015536:Down-Regulation; D005312:Fetal Blood / Q000166:cytology; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: D020413:3' Untranslated Regions; D053631:Interleukin Receptor Common gamma Subunit; D035683:MicroRNAs; D012333:RNA, Messenger