Resveratrol (trans-3,4′,5-trihydroxystilbene), a constituent of red wine, is a natural antioxidant with multiple beneficial health properties that is currently at the stage of preclinical studies for human cancer prevention. Several studies now demonstrate that the protective properties of resveratrol may arise at least in part from its capability to modify the composition of microRNA populations in cells.
1Resveratrol treatment decreases the levels of several oncogenic microRNAs, tumor-suppressor factors such as PDCD4 or PTEN, and key effectors of the TGFβ signaling pathway, while increasing the levels of miR-663, a tumor-suppressor microRNA targeting TGFβ1 transcripts.
While upregulating several components of the TGFβ signaling pathway such as TGFβ receptors type I (TGFβR1) and type II (TGFβR2), resveratrol decreases the transcriptional activity of SMADs, the main effectors of the canonical TGFβ pathway.
2A specific group of microRNAs in the heart that are altered during ischemia/reperfusion injuries can be restored to their basal expression level in mice treated with resveratrol or longevinex [commercial resveratrol formulation]. The target genes for this differentially expressed group of microRNAs include genes of various molecular function such as metal ion binding, sodium-potassium ion, transcription factors, which may play key role in reducing I/R injury.
Rats pretreated with resveratrol for 3 weeks leads to significant cardioprotection against I/R injury.
3In human THP-1 monocytic cells and human blood monocytes, resveratrol upregulates miR-663, a microRNA potentially targeting multiple genes implicated in the immune response.
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.
Manipulating miR-663 levels may help to optimize the use of resveratrol as an anti-inflammatory.
1. Tili E, Michaille JJ, Alder H, Volinia S, Delmas D, Latruffe N, Croce CM. (2010) Resveratrol modulates the levels of microRNAs targeting genes encoding tumor-suppressors and effectors of TGFβ signaling pathway in SW480 cells. Biochem Pharmacol 80(12), 2057-65. [abstract]
2. Mukhopadhyay P, Mukherjee S, Ahsan K, Bagchi A, Pacher P, et al. (2010) Restoration of Altered MicroRNA Expression in the Ischemic Heart with Resveratrol. PLoS ONE 5(12), e15705. [article]
3. Tili E, Michaille JJ, Adair B, Alder H, Limagne E, Taccioli C, Ferracin M, Delmas D, Latruffe N, Croce CM. (2010) Resveratrol decreases the levels of miR-155 by upregulating miR-663, a microRNA targeting JunB and JunD. Carcinogenesis 31(9), 1561-6. [abstract]