Resveratrol suppresses melanoma by inhibiting NF-κB/miR-221 and inducing TFG expression.

Resveratrol (Res) is a natural compound with anti-cancer effects. The goal of this study is to evaluate the suppression of Res in melanoma and investigate its relationship with miRNAs during this process. The in vitro and in vivo anti-cancer abilities of Res were evaluated using cellular assays and animal model. Two melanoma cell lines (A375 and MV3) were used for both in vitro assay and in vivo experiments. qRT-PCR and Western blot were used to detect the changes in gene expressions and protein levels. Dual-luciferase reporter assay and bioinformatic tools were used to further confirm the protein binding and activation of targeted genes. In vitro experiments showed Res significantly decreased the expression of miR-221, an oncogenic microRNA, which was confirmed by the overexpression of miR-221 with or without Res treatment. Mechanistically, we showed that the inhibition of miR-221 by Res was achieved by regulating NF-κB (RELA) activity. In the meantime, we also identified that TFG, a tumor suppressor gene, was a target of miR-221. Finally, using in vivo melanoma model, we confirmed the tumor suppressive effects of Res and our in vitro regulatory network. Res displayed a significant anti-tumor effect on melanoma cells both in vitro and in vivo. The cellular mechanism under this effect involves miRNA regulation.