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Ovarian tumor-associated microRNA-20a decreases natural killer cell cytotoxicity by downregulating MICA/B expression

Cellular & Molecular Immunology volume 11, pages 495–502 (2014)Cite this article

Abstract

MicroRNAs (miRNAs) are a class of small non-coding regulatory RNAs, and changes in miRNAs are involved in tumor origin and progression. Studies have shown that miR-20a is overexpressed in human ovarian cancer tissues and that this miRNA enhances long-term cellular proliferation and invasion capabilities. In this study, a positive correlation between serum miR-20a expression and ovarian cancer stage was observed. We found that miR-20a binds directly to the 3′-untranslated region of MICA/B mRNA, resulting in its degradation and reducing its protein levels on the plasma membrane. Reduction of membrane-bound MICA/B proteins, which are ligands of the natural killer group 2 member D (NKG2D) receptor found on natural killer (NK) cells, γδ+ T cells and CD8+ T cells, allows tumor cells to evade immune-mediated killing. Notably, antagonizing miR-20a action enhanced the NKG2D-mediated killing of tumor cells in both in vitro and in vivo models of tumors. Taken together, our data indicate that increased levels of miR-20a in tumor cells may indirectly suppress NK cell cytotoxicity by downregulating MICA/B expression. These data provide a potential link between metastasis capability and immune escape of tumor cells from NK cells.

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Acknowledgements

This work was supported by the Medical Science and Technology Development Foundation of Nanjing (Department of Health, grant numbers YKK12076 and QRX11243) and the National Natural Science Foundation of China (grant number 81201598). We thank Dr Hui Wang and Professor Yayi Hou for their helpful comments on the manuscript.

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  1. Jingyan Xie and Mengna Liu: Jingyan Xie and Mengna Liu contributed equally to this work.

Authors and Affiliations

  1. Nanjing First Hospital, Nanjing Medical University, Nanjing,, China

    Jingyan Xie, Mengna Liu, Yujuan Li, Qiongyu Mi & Shuli Zhao

  2. State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China

    Shuli Zhao

  3. Immunology and Reproductive Biology Lab of Medical School, Nanjing University, Nanjing, 210093

    Yunzhong Nie & Yunzhong Nie

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  1. Jingyan Xie
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Correspondence to Shuli Zhao.

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Xie, J., Liu, M., Li, Y. et al. Ovarian tumor-associated microRNA-20a decreases natural killer cell cytotoxicity by downregulating MICA/B expression. Cell Mol Immunol 11, 495–502 (2014). https://doi.org/10.1038/cmi.2014.30

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