Yu Y.-H.Chen H.-A.Chen P.-S.Cheng Y.-J.Hsu W.-H.Chang Y.-W.Chen Y.-H.Jan Y.Hsiao M.Chang T.-Y.Liu Y.-H.YUNG-MING JENGWu C.-H.Huang M.-T.Su Y.-H.Hung M.-C.Chien M.-H.Chen C.-Y.Kuo M.-L.Su J.-L.2020-03-062020-03-0620130950-9232https://www.scopus.com/inward/record.uri?eid=2-s2.0-84873056468&doi=10.1038%2fonc.2012.74&partnerID=40&md5=6e5296538866603cc99e159bd509240ahttps://scholars.lib.ntu.edu.tw/handle/123456789/473368Resveratrol, a phytochemical found in various plants and Chinese herbs, is associated with multiple tumor-suppressing activities, has been tested in clinical trials. However, the molecular mechanisms involved in resveratrol-mediated tumor suppressing activities are not yet completely defined. Here, we showed that treatment with resveratrol inhibited cell mobility through induction of the mesenchymal-epithelial transition (MET) in lung cancer cells. We also found that downregulation of FOXC2 (forkhead box C2) is critical for resveratrol-mediated suppression of tumor metastasis in an in vitro and in vivo models. We also identified a signal cascade, namely, resveratrol - |miRNA-520h - |PP2A/C - |Akt → NF-κB → FOXC2, in which resveratrol inhibited the expression of FOXC2 through regulation of miRNA-520h-mediated signal cascade. This study identified a new miRNA-520h-related signal cascade involved in resveratrol-mediated tumor suppression activity and provide the clinical significances of miR-520h, PP2A/C and FOXC2 in lung cancer patients. Our results indicated a functional link between resveratrol-mediated miRNA-520h regulation and tumor suppressing ability, and provide a new insight into the role of resveratrol-induced molecular and epigenetic regulations in tumor suppression. ? 2013 Macmillan Publishers Limited.[SDGs]SDG3immunoglobulin enhancer binding protein; microRNA; microRNA 520h; protein kinase B; resveratrol; transcription factor FOXC2; unclassified drug; animal experiment; animal model; article; cancer cell; cancer growth; cancer inhibition; cancer patient; cell motility; controlled study; down regulation; drug mechanism; enzyme inactivation; epithelial mesenchymal transition; female; human; in vitro study; in vivo study; lung cancer; male; mouse; nonhuman; priority journal; protein expression; regulatory mechanism; signal transduction; Animals; Antineoplastic Agents, Phytogenic; Cell Line; Cell Line, Tumor; Cell Movement; Disease Progression; Down-Regulation; Epithelial-Mesenchymal Transition; Female; Forkhead Transcription Factors; HEK293 Cells; Humans; Lung Neoplasms; Mice; Mice, SCID; MicroRNAs; NF-kappa B; Protein Phosphatase 2; Proto-Oncogene Proteins c-akt; Stilbenes; Xenograft Model Antitumor Assaysjournal article10.1038/onc.2012.74224107812-s2.0-84873056468