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

Cited 89 time in scopus
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Title
Human microRNA-27a* targets Prf1 and GzmB expression to regulate NK-cell cytotoxicity
Author(s)
Tae-Don KimSu Ui Lee; Sohyun Yun; H N Sun; S H Lee; Jae Wha Kim; H M Kim; S K Park; Chang Woo LeeSuk Ran Yoon; P D Greenberg; In Pyo Choi
Bibliographic Citation
Blood, vol. 118, no. 20, pp. 5476-5486
Publication Year
2011
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
Publisher
Amer Soc Hematology
DOI
http://dx.doi.org/10.1182/blood-2011-04-347526
Type
Article
Appears in Collections:
Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
Ochang Branch Institute > Natural Product Research Center > 1. Journal Articles
Ochang Branch Institute > Division of National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
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