상세 정보

underline
Metadata Downloads : dc(xml) or Excel
Cited 0 time in scopus ci

Title 

MicroRNA-150 regulates the cytotoxicity of natural killers by targeting perforin-1

Authors 

Nayoung KimM KimSohyun YunJ DohP D GreenbergTae-Don KimIn Pyo Choi

Publisher 

Elsevier

Issue Date 

2014

Citation 

Journal of Allergy and Clinical Immunology, vol. 134, no. 1, pp. 195-203

Keywords 

immunotherapymiR-150NK cell cytotoxicityNK cellsperforin-1post-transcriptional regulationtumor growth and metastasis

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 3′ 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.

ISSN 

0091-6749

Link 

http://dx.doi.org/10.1016/j.jaci.2014.02.018

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


There are no files associated with this item.
qrcode

FusionCharts.
DSpace Software Coptright(c) 2010 MIT and Hewleft-Packard  /  KRIBB-REPOSITORY ( Email:jakim@kribb.re.kr)