title: MicroRNA-200b reverses chemoresistance of docetaxel-resistant human lung adenocarcinoma cells by targeting E2F3.
abstract: BACKGROUND
  MicroRNAs (miRNAs) have been identified as important posttranscriptional regulators involved in various biological and pathological processes of cells, but their association with tumor chemoresistance has not been fully understood.
  
  
  METHODS
  We detected miRNA-200b (miR-200b) expression in different lung adenocarcinoma cell lines and then focused on its roles in regulation of docetaxel chemoresistance. We also identified E2F3 as a novel target of miR-200b.
  
  
  RESULTS
  Based on miRNA microarray data, miR-200b was identified as the most down-regulated miRNA in docetaxel-resistant SPC-A1/DTX cells compared with parental SPC-A1 cells. Ectopic miR-200b expression reversed docetaxel chemoresistance of lung adenocarcinoma cells through cell proliferation inhibition, apoptosis enhancement, and G(2) /M cell cycle arrest. In a nude mouse xenograft model, up-regulation of miR-200b significantly enhanced response of SPC-A1/DTX cells to docetaxel. Luciferase reporters containing the 3' untranslated region sequence of E2F3 messenger RNA were used to demonstrate that miR-200b could directly target E2F3. Small interfering RNA-mediated E2F3 knockdown revealed similar effects as that of ectopic miR-200b expression. Decreased miR-200b expression was also detected in tumor tissues sampled from lung adenocarcinoma patients treated with docetaxel-based chemotherapy and was proved to be correlated with high expression of E2F3, decreased sensitivity to docetaxel, and poor prognosis.
  
  
  CONCLUSIONS
  Our results suggest that down-regulation of miR-200b could lead to E2F3 overexpression and in turn contribute to chemoresistance of lung adenocarcinoma cells to docetaxel.
authors.affiliation: Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Feng
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Hai-Zhu
authors.initials: HZ
authors.lastname: Song
authors.forename: Long-Bang
authors.initials: LB
authors.lastname: Chen
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics*; D000077192:Adenocarcinoma of Lung; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D000077143:Docetaxel; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D050699:E2F3 Transcription Factor; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D011379:Prognosis; D043823:Taxoids / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D050699:E2F3 Transcription Factor; C098319:E2F3 protein, human; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D043823:Taxoids; D000077143:Docetaxel