title: Cutting edge: microRNA-181 promotes human NK cell development by regulating Notch signaling.
abstract: MicroRNAs (miRs) have recently been identified as important regulators of gene expression at the posttranscriptional level. Although it has clearly been established that miRs influence the ontogeny of several immune cell lineages, the role of individual miRs during NK cell development has not been described. In this study, we show that miR-181 expression levels have a profound impact on the development of human NK cells from CD34(+) hematopoietic progenitor cells and IFN-γ production in primary CD56(+) NK cells. We also demonstrate that nemo-like kinase (NLK), an inhibitor of Notch signaling, is a target of miR-181 in NK cells, and knockdown of NLK mirrors the developmental effect of miR-181 overexpression. We conclude that miR-181 promotes NK cell development, at least in part, through the suppression of NLK, providing an important link between miRs and Notch signaling.
authors.affiliation: Division of Hematology, Oncology, and Transplantation, University of Minnesota Cancer Center, Minneapolis, MN 55455, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Cichocki
authors.forename: Martin
authors.initials: M
authors.lastname: Felices
authors.forename: Valarie
authors.initials: V
authors.lastname: McCullar
authors.forename: Steven R
authors.initials: SR
authors.lastname: Presnell
authors.forename: Ahmad
authors.initials: A
authors.lastname: Al-Attar
authors.forename: Charles T
authors.initials: CT
authors.lastname: Lutz
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Miller
mesh_terms: D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism*; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D051880:Receptors, Notch / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C540193:MIrn181 microRNA, human; D035683:MicroRNAs; D051880:Receptors, Notch; C470551:NLK protein, human; D017346:Protein Serine-Threonine Kinases
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