title: Cutting edge: down-regulation of MHC class I-related chain A on tumor cells by IFN-gamma-induced microRNA.
abstract: NKG2D is a receptor used by NK cells to detect virally infected and transformed cells. It recognizes ligands that are expressed constitutively on primary tumors and tumor cell lines. In this report, we have identified four microRNAs (miRNAs) that each was sufficient to reduce the expression of the NKG2D ligand MHC class I-related chain A (MICA). One of these miRNAs (miR-520b) was induced by IFN-gamma, leading to a reduction in MICA surface protein levels. Interestingly, miR-520b acted on both the MICA 3'-untranslated region and the promoter region and caused a decrease in the levels of MICA transcript. In contrast, an antisense oligonucleotide inhibitor of miR-520b increased the expression of a reporter construct containing the MICA 3'-untranslated region but not the MICA promoter region. These findings demonstrate the novel regulation of an NKG2D ligand by an endogenous microRNA that is itself induced by IFN-gamma.
authors.affiliation: Department of Pathology, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Deepak
authors.initials: D
authors.lastname: Yadav
authors.forename: Jennifer
authors.initials: J
authors.lastname: Ngolab
authors.forename: Rod Seung-Hwan
authors.initials: RS
authors.lastname: Lim
authors.forename: Siddharth
authors.initials: S
authors.lastname: Krishnamurthy
authors.forename: Jack D
authors.initials: JD
authors.lastname: Bui
mesh_terms: D020413:3' Untranslated Regions / Q000037:antagonists & inhibitors; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000235:genetics* / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D045325:HCT116 Cells; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology*; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000276:immunology; D013489:Suppression, Genetic / Q000276:immunology
chemical_list: D020413:3' Untranslated Regions; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A; D035683:MicroRNAs; D007371:Interferon-gamma