Stern-Ginossar Noam, Gur Chamutal, Biton Moshe, Horwitz Elad, Elboim Moran, Stanietsky Noa, Mandelboim Michal, Mandelboim Ofer
Lautenberg Center for General and Tumor Immunology, The Hebrew University, The BioMedical Research Institute, Hadassah Medical School, Jerusalem 91120, Israel.
Nat Immunol. 2008 Sep;9(9):1065-73. doi: 10.1038/ni.1642.
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.
MICA和MICB是由激活受体NKG2D识别的应激诱导配体。人巨细胞病毒编码的一种微小RNA通过靶向MICB 3'非翻译区的特定位点下调MICB表达。由于该位点在不同的MICB等位基因中保守，且在MICA 3'非翻译区存在类似位点，我们推测这些位点被细胞微小RNA靶向。在此，我们鉴定了与这些MICA和MICB 3'非翻译区序列结合的微小RNA，并获得数据表明这些微小RNA在一定阈值下维持MICA和MICB蛋白的表达，并在细胞应激期间促进MICA和MICB的急性上调。这些微小RNA在各种肿瘤中过表达，我们在此证明它们有助于肿瘤逃避免疫识别。
