title: Upregulation of microRNA-451 increases cisplatin sensitivity of non-small cell lung cancer cell line (A549).
abstract: BACKGROUND
  Recently, miR-451 as a tumor suppressor has been reported in other studies. However, whether miR-451 can affect the sensitivity of non-small cell lung cancer (NSCLC) cells to cisplatin (DDP) remains unclear. The aim of this study is to evaluate the roles of miR-451 in the sensitivity of NSCLC cells to DDP.
  
  
  METHODS
  Quantitative RT-PCR assay was performed to detect the expression of miR-451 in 10 pairs of NSCLC and noncancerous tissue samples. pcDNA-GW/EmGFP-miR-451 was stably transfected into NSCLC cell line (A549). Then, the effects of miR-451 upregulation on growth, colony formation and apoptosis of A549 cells were investigated. Finally, the effects of miR-451 upregulation on in vitro and in vivo sensitivity of A549 cells of DDP were also determined.
  
  
  RESULTS
  The level of miR-451 expression in NSCLC tissues was significantly higher than that in corresponding noncancerous tissues. Ectopic overexpression of miR-451 could significantly inhibit growth and induce apoptosis of A549 cells. Moreover, ectopic overexpression of miR-451 could sensitize A549 cells to DDP possibly by increasing DDP-induced apoptosis which might be associated with the inactivation of Akt signaling pathway.
  
  
  CONCLUSIONS
  This study demonstrated for the first time that combination of DDP application with miR-451 upregulation might be a potential strategy for the treatment of human NSCLC.
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiangjiayuan Road, Nanjing 210011, China.
authors.forename: Hai-Bo
authors.initials: HB
authors.lastname: Bian
authors.forename: Xuan
authors.initials: X
authors.lastname: Pan
authors.forename: Jin-Song
authors.initials: JS
authors.lastname: Yang
authors.forename: Zhao-Xia
authors.initials: ZX
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: De
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D005562:Formazans; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D013778:Tetrazolium Salts; D014162:Transfection; D015854:Up-Regulation / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D005562:Formazans; C531201:MIRN451 microRNA, human; D035683:MicroRNAs; D013778:Tetrazolium Salts; C079782:MTT formazan; D002945:Cisplatin