MiR-10b downregulates the stress-induced cell surface molecule MICB, a critical ligand for cancer cell recognition by natural killer cells

Pinchas Tsukerman, Noam Stern-Ginossar, Chamutal Gur, Ariella Glasner, Daphna Nachmani, Yoav Bauman, Rachel Yamin, Alon Vitenshtein, Noah Stanietsky, Tomer Bar-Mag, Dikla Lankry, Ofer Mandelboim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

107 Scopus citations

Abstract

Natural killer cells (NK) are a component of innate immunity well known for their potent ability to kill virusinfected or neoplastically transformed cells following stimulation of the NK cell receptor NKG2D. One of the various ligands of NKG2D is MICB, a stress-induced ligand that has been found to be upregulated on the surface of tumor cells. However, there is little knowledge about how this upregulation may occur or how it may be selected against in tumors as a mechanism of immune escape. Here, we report that the metastasis-associated microRNA (metastamir) miR-10b directly binds to the 3' untranslated region of MICB and downregulates its expression. Notably, antagonizing miR-10b action enhanced NKG2D-mediated killing of tumor cells in vitro and enhanced clearance of tumors in vivo. Conversely, overexpression of miR-10b downregulatedMICBand impaired elimination of tumor cells. Together, our results define MICB as a novel immune target of miR-10b, implying a direct link between metastasis capability and immune escape from NK cells.

Original languageAmerican English
Pages (from-to)5463-5472
Number of pages10
JournalCancer Research
Volume72
Issue number21
DOIs
StatePublished - 1 Nov 2012

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