Human microRNAs regulate stress-induced immune  responses mediated by the receptor NKG2D.
MICA and MICB are stress-induced ligands recognized by the activating receptor NKG2D. A microRNA encoded by human cytomegalovirus downregulates MICB expression by targeting a specific site in the MICB 3' untranslated region. As this site is conserved among different MICB alleles and a similar site exists in the MICA 3' untranslated region, we speculated that these sites are targeted by cellular microRNAs. Here we identified microRNAs that bound to these MICA and MICB 3' untranslated region sequences and obtained data suggesting that these microRNAs maintain expression of MICA and MICB protein under a certain threshold and facilitate acute upregulation of MICA and MICB during cellular stress. These microRNAs were overexpressed in various tumors and we demonstrate here that they aided tumor avoidance of immune recognition.
Stern-Ginossar
Noam
N
Lautenberg Center for General and Tumor Immunology, The Hebrew University, The BioMedical Research Institute, Hadassah Medical School, Jerusalem 91120, Israel.
Gur
Chamutal
C
Biton
Moshe
M
Horwitz
Elad
E
Elboim
Moran
M
Stanietsky
Noa
N
Mandelboim
Michal
M
Mandelboim
Ofer
O
D000954:Antigens, Surface / Q000378:metabolism; D002460:Cell Line; D005822:Genetic Vectors; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000276:immunology / Q000502:physiology*; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic / Q000378:metabolism*; D055607:Receptors, Natural Killer Cell; D013312:Stress, Physiological / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D000954:Antigens, Surface; D015395:Histocompatibility Antigens Class I; C527085:KLRK1 protein, human; C099187:MHC class I-related chain A; C098080:MICB antigen; D035683:MicroRNAs; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell