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 NK-cell 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.
journal_name
Bloodjournal_title
Bloodauthors
Kim TD,Lee SU,Yun S,Sun HN,Lee SH,Kim JW,Kim HM,Park SK,Lee CW,Yoon SR,Greenberg PD,Choi Idoi
10.1182/blood-2011-04-347526subject
Has Abstractpub_date
2011-11-17 00:00:00pages
5476-86issue
20eissn
0006-4971issn
1528-0020pii
blood-2011-04-347526journal_volume
118pub_type
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