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Cutting Edge: Down-Regulation of MHC Class I-Related Chain A on Tumor Cells by IFN--Induced MicroRNA¹

Department of Pathology, University of California, San Diego, La Jolla, CA 92093

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-, 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-.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by grants to J.D.B. from the American Cancer Society (ACS Institutional Research Grant 70-002) and the Cancer Research Coordinating Committee (6-444951-34384) and by the V Foundation Scholar Award.

² D.Y. and J.N. contributed equally to this paper.

³ Address correspondence and reprint requests to Dr. Jack D. Bui, 9500 Gilman Drive, Department of Pathology, University of California, San Diego, La Jolla, CA 92093. E-mail address: jbui{at}ucsd.edu

⁴ Abbreviations used in this paper: MIC, MHC class I-related chain; miRNA, microRNA; UTR, untranslated region.

⁵ The online version of this article contains supplemental material.

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