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Title 

Human microRNA-27a* targets Prf1 and GzmB expression to regulate NK-cell cytotoxicity

Authors 

Tae-Don KimSu Ui LeeSohyun YunH N SunS H LeeJae Wha KimH M KimS K ParkChang Woo LeeSuk Ran YoonP D GreenbergIn Pyo Choi

Publisher 

American Society of Hematology

Issue Date 

2011

Citation 

Blood, vol. 118, no. 20, pp. 5476-5486

Abstract 

Perforin (Prf1) and granzyme B (GzmB) are essential effector molecules for natural killer (NK)-cell cytotoxicity, but how Prf1 and GzmB expression is regulated during arming of NK cells is poorly defined. We show that human microRNA (miR)-27a*is a negative regulator of NKcell cytotoxicity by silencing Prf1 and GzmB expression. Human miR-27a*specifically bound to the 3′ untranslated regions of Prf1 and GzmB, down-regulating expression in both resting and activated NK cells, and it functioned as a fine-tuner for homeostasis of the net amount of the effector proteins. Consistent with miR-27a*having an inhibitory role, knockdown of miR-27a*in NK cells dramatically increased cytotoxicity in vitro and decreased tumor growth in a human tumor xenograft model. Thus, NK-cell cytotoxicity is regulated, in part, by microRNA, and modulating endogenous miR-27a*levels in NK cells represents a potential immunotherapeutic strategy.

ISSN 

0006-4971

Link 

http://dx.doi.org/10.1182/blood-2011-04-347526

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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