title: MicroRNA-138 regulates chemoresistance in human non-small cell lung cancer via epithelial mesenchymal transition.
abstract: OBJECTIVE
  Down-regulation of miR-138 is observed in a variety of cancers, which suggests that miR-138 may be involved in cancer pathogenesis. Our current work aimed to evaluate the effects of miR-138 in adriamycin (ADM)-resistant human NSCLC cells.
  
  
  METHODS
  Cell proliferation was determined by MTT assay. Real-time PCR and western blot were performed to detect the mRNA and protein expression levels. The target of miR-138 was validated by luciferase activity assay.
  
  
  RESULTS
  Compared with the chemosensitive parental cells, miR-138 was remarkably decreased in A549/ADM and NCI-H23/ADM cells. Ectopic expression of miR-138 sensitized chemoresistant tumor cells to ADM administration. In addition, the epithelial-mesenchymal transition (EMT) related markers E-cadherin or vimentin was up-regulated or down-regulated upon the overexpression of miR-138 in NSCLC cells. Further studies identified zinc finger E-box-binding homeobox 2 (ZEB2) as the target of miR-138 and up-regulation of miR-138 suppressed the mRNA and protein expression of ZEB2. Notably, luciferase reporter assay confirmed that ZEB2 was a direct target of miR-138.
  
  
  CONCLUSIONS
  Our study demonstrates that miR-138 sensitizes NSCLC cells to ADM via EMT, suggesting that miR-138 might be a potential therapeutic target for drug-resistant NSCLC patients.
authors.affiliation: Institute of Respiratory Disease, China Three Gorges University, Yichang Central People's Hospital, China. 222xiaozhao@163.com.
authors.forename: Z
authors.initials: Z
authors.lastname: Jin
authors.forename: L
authors.initials: L
authors.lastname: Guan
authors.forename: Y
authors.initials: Y
authors.lastname: Song
authors.forename: G-M
authors.initials: GM
authors.lastname: Xiang
authors.forename: S-X
authors.initials: SX
authors.lastname: Chen
authors.forename: B
authors.initials: B
authors.lastname: Gao
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology* / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000502:physiology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics*; D035683:MicroRNAs / Q000502:physiology*
chemical_list: D000903:Antibiotics, Antineoplastic; C546110:MIRN138 microRNA, human; D035683:MicroRNAs; D004317:Doxorubicin