1. Human microRNA-27a* targets Prf1 and GzmB expression to regulate NK-cell cytotoxicity.
- Author
-
Kim, Tae-Don, Lee, Su Ui, Yun, Sohyun, Sun, Hu-Nan, Lee, Suk Hyung, Kim, Jae Wha, Kim, Hwan Mook, Park, Song-Kyu, Lee, Chang Woo, Yoon, Suk Ran, Greenberg, Philip D., and Choi, Inpyo
- Subjects
- *
MICRORNA , *KILLER cells , *CELL-mediated cytotoxicity , *HOMEOSTASIS , *TUMOR growth , *XENOGRAFTS - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF