title: Human microRNA-1245 down-regulates the NKG2D receptor in natural killer cells and impairs NKG2D-mediated functions.
abstract: BACKGROUND
  NKG2D is an activating receptor expressed by natural killer and T cells, which have crucial functions in tumor and microbial immunosurveillance. Several cytokines have been identified as modulators of NKG2D receptor expression. However, little is known about NKG2D gene regulation. In this study, we found that microRNA 1245 attenuated the expression of NKG2D in natural killer cells.
  
  
  METHODS
  We investigated the potential interactions between the 3'-untranslated region of the NKG2D gene and microRNA as well as their functional roles in the regulation of NKG2D expression and cytotoxicity in natural killer cells.
  
  
  RESULTS
  Transforming growth factor-β1, a major negative regulator of NKG2D expression, post-transcriptionally up-regulated mature microRNA-1245 expression, thus down-regulating NKG2D expression and impairing NKG2D-mediated immune responses in natural killer cells. Conversely, microRNA-1245 down-regulation significantly increased the expression of NKG2D expression in natural killer cells, resulting in more efficient NKG2D-mediated cytotoxicity. CONCLUSIONS These results reveal a novel NKG2D regulatory pathway mediated by microRNA-1245, which may represent one of the mechanisms used by transforming growth factor-β1 to attenuate NKG2D expression in natural killer cells.
authors.affiliation: Department of Hematology and Oncology, Kanazawa University Hospital 13-1 Takaramachi, Kanazawa, 920-8641, Japan.
authors.forename: J Luis
authors.initials: JL
authors.lastname: Espinoza
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Takami
authors.forename: Katsuji
authors.initials: K
authors.lastname: Yoshioka
authors.forename: Katsuya
authors.initials: K
authors.lastname: Nakata
authors.forename: Tokiharu
authors.initials: T
authors.lastname: Sato
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Kasahara
authors.forename: Shinji
authors.initials: S
authors.lastname: Nakao
mesh_terms: D015153:Blotting, Western; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism / Q000473:pathology*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D009690:Nucleic Acid Conformation; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D055655:NK Cell Lectin-Like Receptor Subfamily K; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D053773:Transforming Growth Factor beta1