Human microRNAs regulate stress-induced immune responses mediated by the receptor NKG2D
Human microRNAs regulate stress-induced immune responses mediated by the receptor NKG2D
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DOI：
10.1038/ni.1642
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发表时间：
2008-09-01
影响因子：
30.5
通讯作者：
Mandelboim, Ofer
中科院分区：
文献类型：
--
作者：
Stern-Ginossar, Noam;Gur, Chamutal;Mandelboim, Ofer
云母和MICB是由活化受体NKG2D识别的应激诱导配体。由人巨细胞病毒编码的微小RNA通过靶向MICB 3'非翻译区中的特定位点来下调MICB表达。由于该位点在不同的MICB等位基因中是保守的，并且在云母3'非翻译区中存在类似的位点，我们推测这些位点被细胞microRNA靶向。在此，我们鉴定了与这些云母和MICB 3'非翻译区序列结合的microRNA，并且获得的数据表明这些microRNA在一定阈值下维持云母和MICB蛋白的表达，并且在细胞应激期间促进云母和MICB的急性上调。这些microRNA在各种肿瘤中过表达，我们在这里证明它们有助于肿瘤避免免疫识别。
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.