title: MiR-520h-mediated FOXC2 regulation is critical for inhibition of lung cancer progression by resveratrol.
abstract: Resveratrol, 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.
authors.affiliation: Department of Internal Medicine, Divisions of Pulmonary and Critical Care Medicine, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Y-H
authors.initials: YH
authors.lastname: Yu
authors.forename: H-A
authors.initials: HA
authors.lastname: Chen
authors.forename: P-S
authors.initials: PS
authors.lastname: Chen
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Cheng
authors.forename: W-H
authors.initials: WH
authors.lastname: Hsu
authors.forename: Y-W
authors.initials: YW
authors.lastname: Chang
authors.forename: Y-H
authors.initials: YH
authors.lastname: Chen
authors.forename: Y
authors.initials: Y
authors.lastname: Jan
authors.forename: M
authors.initials: M
authors.lastname: Hsiao
authors.forename: T-Y
authors.initials: TY
authors.lastname: Chang
authors.forename: Y-H
authors.initials: YH
authors.lastname: Liu
authors.forename: Y-M
authors.initials: YM
authors.lastname: Jeng
authors.forename: C-H
authors.initials: CH
authors.lastname: Wu
authors.forename: M-T
authors.initials: MT
authors.lastname: Huang
authors.forename: Y-H
authors.initials: YH
authors.lastname: Su
authors.forename: M-C
authors.initials: MC
authors.lastname: Hung
authors.forename: M-H
authors.initials: MH
authors.lastname: Chien
authors.forename: C-Y
authors.initials: CY
authors.lastname: Chen
authors.forename: M-L
authors.initials: ML
authors.lastname: Kuo
authors.forename: J-L
authors.initials: JL
authors.lastname: Su
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D018450:Disease Progression; D015536:Down-Regulation / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000235:genetics; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D054648:Protein Phosphatase 2 / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051858:Forkhead Transcription Factors; D035683:MicroRNAs; D016328:NF-kappa B; D013267:Stilbenes; C082078:mesenchyme fork head 1 protein; D051057:Proto-Oncogene Proteins c-akt; D054648:Protein Phosphatase 2; D000077185:Resveratrol