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- Title
Resveratrol decreases the levels of miR-155 by upregulating miR-663, a microRNA targeting JunB and JunD.
- Authors
Tili, Esmerina; Michaille, Jean-Jacques; Adair, Brett; Alder, Hansjuerg; Limagne, Emeric; Taccioli, Cristian; Ferracin, Manuela; Delmas, Dominique; Latruffe, Norbert; Croce, Carlo M.
- Abstract
An inflammatory component is present in the microenvironment of most neoplastic tissues, including those not causally related to an obvious inflammatory process. Several microRNAs, and especially miR-155, play an essential role in both the innate and adaptative immune response. Resveratrol (trans-3,4′,5-trihydroxystilbene) is a natural antioxidant with anti-inflammatory properties that is currently at the stage of preclinical studies for human cancer prevention. Here, we establish that, in human THP-1 monocytic cells as well as in human blood monocytes, resveratrol upregulates miR- 663, a microRNA potentially targeting multiple genes implicated in the immune response. In THP-1 cells, miR-663 decreases endogenous activator protein-1 (AP-1) activity and impairs its upregulation by lipopolysaccharides (LPS), at least in part by directly targeting JunB and JunD transcripts. We further establish that the downregulation of AP-1 activity by resveratrol is miR-663 dependent and that the effects of resveratrol on both AP-1 activity and JunB levels are dose dependent. Finally, we show that resveratrol impairs the upregulation of miR-155 by LPS in a miR-663-dependentmanner. Given the role of miR-155 in the innate immune response and the fact that it is upregulated in many cancers, our results suggest that manipulating miR-663 levels may help to optimize the use of resveratrol as both an anti-inflammatory and anticancer agent against malignancies associated with high levels of miR-155.
- Subjects
TISSUES; INFLAMMATION prevention; CANCER diagnosis; IMMUNE response; CANCER treatment
- Publication
Carcinogenesis, 2010, Vol 31, Issue 9, p1561
- ISSN
0143-3334
- Publication type
Article
- DOI
10.1093/carcin/bgq143