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Cutting Edge: Down-Regulation of MHC Class I-Related Chain A on Tumor Cells by IFN-γ-Induced MicroRNA

Deepak YadavDepartment of Pathology, University of California , San Diego, La Jolla, CA 92093Jennifer NgolabDepartment of Pathology, University of California , San Diego, La Jolla, CA 92093Rod Seung-Hwan LimDepartment of Pathology, University of California , San Diego, La Jolla, CA 92093Siddharth R. KrishnamurthyDepartment of Pathology, University of California , San Diego, La Jolla, CA 92093Jack D. BuiDepartment of Pathology, University of California , San Diego, La Jolla, CA 92093

2009en

ABI

Annotatsiya

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.

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Identifikatorlar

DOI: 10.4049/jimmunol.182.1.39

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