MicroRNAs regulate NKG2D ligands on tumor cells (88.21)

Abstract

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. 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). These include miR-106b, -302b, -372, and -520b. Interestingly, mir-372 was also found to reduce the expression of another NKG2D ligand, UL-16 binding protein 2 (ULBP2). One of these miRNAs (miR-520b) was induced by IFN-gamma, leading to a reduction in MICA surface protein levels. 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 NKG2D ligands by endogenous microRNAs.