Resveratrol decreases the levels of miR-155 by upregulating miR-663, a microRNA targeting JunB and JunD.

Esmerina Tili (1) , Jean-Jacques Michaille (2) , Brett Adair (1) , Hansjuerg Alder (1) , Emeric Limagne (2) , Cristian Taccioli (3) , Manuela Ferracin (3) , Dominique Delmas (2) , Norbert Latruffe (2) , Carlo M Croce (1)

1 OSU - Ohio State University [Columbus]
2 LBMC - Laboratoire de Biochimie Moléculaire et Cellulaire
3 Dipartimento di Medicina sperimentale e diagnostica

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 pre-clinical 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 AP-1 activity and impairs its upregulation by 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 anti-cancer agent against malignancies associated with high levels of miR-155.

Domaines: Biochimie, Biologie Moléculaire

Esmerina Tili, Jean-Jacques Michaille, Brett Adair, Hansjuerg Alder, Emeric Limagne, et al.. Resveratrol decreases the levels of miR-155 by upregulating miR-663, a microRNA targeting JunB and JunD.. Carcinogenesis / CARCINOGENESIS(LONDON); Carcinogenesis (Oxford), 2010, epub ahead of print. ⟨10.1093/carcin/bgq143⟩. ⟨hal-00514095⟩