title: Decitabine reverses TGF-β1-induced epithelial-mesenchymal transition in non-small-cell lung cancer by regulating miR-200/ZEB axis.
abstract: OBJECTIVE
  Epithelial-mesenchymal transition (EMT) is a crucial driver of tumor progression. Tumor growth factor-beta 1 (TGF-β1) is an important factor in EMT induction in tumorigenesis. The targeting of EMT may, therefore, represent a promising approach in anticancer treatment.
  
  
  METHODS
  In this study, we determined the effect of decitabine, a DNA methyltransferase inhibitor, on TGF-β1-induced EMT in non-small-cell lung cancer (NSCLC) PC9 and A549 cells. We also assessed the involvement of the miR-200/ZEB axis.
  
  
  RESULTS
  Decitabine reversed TGF-β1-induced EMT in PC9 cells, but not in A549 cells. This phenomenon was associated with epigenetic changes in the miR-200 family, which regulated EMT by altering the expression ofZEB1andZEB2. TGF-β1 induced aberrant methylation in miR-200 promoters, leading to EMT in PC9 cells. Decitabine attenuated this effect and inhibited tumor cell migration in vitro and in vivo. In A549 cells, however, neither TGF-β1 nor decitabine exhibited an effect on miR-200 promoter methylation.
  
  
  CONCLUSIONS
  Our findings suggest that epigenetic regulation of the miR-200/ZEB axis is responsible for EMT induction by TGF-β1 in PC9 cells. Decitabine inhibits EMT in NSCLC cell PC9 through its epigenetic-based therapeutic activity.
authors.affiliation: Department of Medical Oncology, Cancer Center, Lung Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, Cancer Center, Lung Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Yanyang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Medical Oncology, Cancer Center, Lung Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Yuyi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Cancer Center, Lung Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Maoyuan
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Medical Oncology, Cancer Center, Lung Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Tu
authors.affiliation: Department of Medical Oncology, Cancer Center, Lung Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Feng
authors.initials: F
authors.lastname: Luo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001374:Azacitidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D000077209:Decitabine; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D000071799:Zinc Finger E-box-Binding Homeobox 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D053773:Transforming Growth Factor beta1; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; D000077209:Decitabine; D001374:Azacitidine
keywords: DNA methyltransferase inhibitor; EMT; NSCLC; epigenetics; miRNA