MicroRNA-150 regulates the cytotoxicity of natural killers by targeting perforin-1
SCIE
SCOPUS
- Title
- MicroRNA-150 regulates the cytotoxicity of natural killers by targeting perforin-1
- Authors
- Nayoung Kim; Miju Kim; Sohyun Yun; Doh, J; Philip D. Greenber; Tae-Don Kim; Inpyo Choi
- Date Issued
- 2014-07
- Publisher
- Mosby Inc.
- Abstract
- Background: Perforin-1 (Prf1) is the predominant cytolytic protein secreted by natural killer (NK) cells. For a rapid immune response, resting NK cells contain high Prf1 mRNA concentrations while exhibiting minimal cytotoxicity caused by a blockage of Prf1 protein synthesis, implying that an unknown posttranscriptional regulatory mechanism exists. Objective: We sought to determine whether microRNA-150 (miR-150) posttranscriptionally regulates Prf1 translation in both mouse and human NK cells at rest and at various time points after activation. Methods: Mouse NK cells with a targeted deletion of miR-150 (miR-150(-/-) NK cells), primary human NK cells, and NK92 MI cells were used to investigate the role of miR-150 in NK cells. NK cell cytotoxicity assays and Western blotting proved that activated miR-150(-/-) NK cells expressed upregulated Prf1, augmenting NK cell cytotoxicity. When immunodeficient mice were injected with miR-150(-/-) NK cells, there was a significant reduction in tumor growth and metastasis of B16F10 melanoma. Results: We report that miR-150 binds to 39 untranslated regions of mouse and human Prf1, posttranscriptionally downregulating its expression. Mouse wild-type NK cells displayed downregulated miR-150 expression in response to IL-15, which led to corresponding repression and induction of Prf1 during rest and after IL-15 activation, respectively. Conclusion: Our results indicate that miR-150 is a common posttranscriptional regulator for Prf1 in mouse and human NK cells that represses NK cell lytic activity. Thus the therapeutic control of miR-150 in NK cells could enhance NK cell-based immunotherapy against cancer, providing a better clinical outcome.
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/27288
- DOI
- 10.1016/J.JACI.2014.02.018
- ISSN
- 0091-6749
- Article Type
- Article
- Citation
- Journal of Allergy and Clinical Immunology, vol. 134, no. 1, page. 195 - +, 2014-07
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