Journal Article

Resveratrol decreases the levels of miR-155 by upregulating miR-663, a microRNA targeting <i>JunB</i> and <i>JunD</i>

Esmerina Tili, Jean-Jacques Michaille, Brett Adair, Hansjuerg Alder, Emeric Limagne, Cristian Taccioli, Manuela Ferracin, Dominique Delmas, Norbert Latruffe and Carlo M. Croce

in Carcinogenesis

Volume 31, issue 9, pages 1561-1566
Published in print September 2010 | ISSN: 0143-3334
Published online July 2010 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgq143
Resveratrol decreases the levels of miR-155 by upregulating miR-663, a microRNA targeting JunB and JunD

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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-dependent manner. 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.

Journal Article.  4780 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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