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

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-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.

Epigenetic changes induced by curcumin and other natural compounds

“…In these cells, resveratrol improved the action of adenosine analogues to inhibit methylation and to increase expression of the retinoic acid receptor beta 2 gene (Stefanska et al 2010). In addition, resveratrol decreased the levels of the miR-155 by up-regulating miR-663, an miRNA targeting JunB and JunD (Tili et al 2010a), and modulated expression levels of miRNA target genes, such as tumor suppressors and effectors of the transforming growth factor-b signaling pathway, in SW480 cells (Tili et al 2010b).…”

MiR-663, a microRNA targeting p21WAF1/CIP1, promotes the proliferation and tumorigenesis of nasopharyngeal carcinoma

“…It is upregulated by oscillatory shear stress and has a key role in oscillatory shear-induced inflammatory responses by mediating the expression of the inflammatory gene network in human umbilical vein endothelial cells (Ni et al, 2011). In human THP-1 monocytic cells and human blood monocytes, resveratrol upregulates miR-663, which decreases endogenous activator protein-1 activity and impairs its upregulation by lipopolysaccharides by targeting Jun B and Jun D (Tili et al, 2010a). Furthermore, it is involved in a resveratrolrelevant pathway by targeting transforming growth factor-b1 (Tili et al, 2010b).…”

Wortmannin as Targeted Therapeutic Agent for the Treatment of Triple-Negative Breast Cancer

“…The results obtained in the present study showed that wortmannin induces expression of miRs and thus acts as suppresser of tumor growth. It has been reported that miRs exhibits anti-carcinoma effect on tumor growth by interfering with the expression of Jun B and Jun D [19]. miR 19 suppresses the expression of tissue factor which is involved in the progress of tumors [20].…”