Cutting edge: down-regulation of MHC class I-related chain A on tumor cells by IFN-gamma-induced microRNA.

Cutting edge: down-regulation of MHC class I-related chain A on tumor cells by IFN-gamma-induced microRNA.
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DOI:
10.4049/jimmunol.182.1.39
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发表时间:
2009-01-01
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Bui JD
Bui JD
中科院分区:
其他
文献类型:
--
作者:
Yadav D;Ngolab J;Lim RS;Krishnamurthy S;Bui JD

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NKG2D是自然杀伤(NK)细胞用来检测病毒感染和转化细胞的受体。它识别在原发肿瘤和肿瘤细胞系上组成性表达的配体。在这份报告中,我们已经鉴定出四个microRNAs(MiRNAs),每个都足以降低NKG2D配体主要组织相容性复合体I类相关链A(MICA)的表达。其中一个miRNAs(miR-520B)是由干扰素γ诱导的,导致MICA表面蛋白水平降低。有趣的是,miR-520B同时作用于MICA 3‘非编码区和启动子区域,并导致MICA转录本水平下降。相反,miR-520B的反义寡核苷酸抑制剂增加了含有MICA 3‘UTR而不是MICA启动子区域的报告结构的表达。这些发现证明了由干扰素γ诱导的内源性miRNA对NKG2D配体的新调节。
NKG2D is a receptor used by natural killer (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 major histocompatibility complex class I-related chain A (MICA). One of these miRNAs (miR-520b) was induced by IFNγ, leading to a reduction in MICA surface protein levels. Interestingly, miR-520b acted on both the MICA 3′UTR and promoter region and caused a decrease in the levels of MICA transcript. In contrast, an anti-sense oligonucleotide inhibitor of miR-520b increased the expression of a reporter construct containing the MICA 3′UTR but not the MICA promoter region. These findings demonstrate the novel regulation of an NKG2D ligand by an endogenous miRNA that is itself induced by IFNγ.
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