title: [EGFR-ERK signaling pathway down-regulates miRNA-145 in lung cancer cells].
abstract: OBJECTIVE
  To investigate the relationship between EGFR activation and down-regulation of miRNA-145 in lung cancer.
  
  
  METHODS
  Normal human lung epithelia cell line (BEAS-2B), human lung adenocarcinoma cell lines with wild-type EGFR (A549 and H292) and human lung adenocarcinoma cell lines with EGFR mutation (H1975 and H1650) were chosen in this study. The levels of miRNA-145 and p-EGFR were determined by quantitative real-time PCR (qRT-PCR) and Western blotting, respectively, and the relationship between p-EGFR and miRNA-145 levels was analyzed. The miRNA-145 levels were determined by qRT-PCR after activating EGFR with EGF or blocking EGFR signal pathway with AG1478. In addition, ERK1/2 inhibitor U0126 was used to inhibit ERK1/2 activation and then the expression of miRNA-145 was detected.
  
  
  RESULTS
  The miRNA-145 levels were closely negatively related with p-EGFR in lung cancer cells (r = -0.926, P = 0.024). EGF down-regulated miRNA-145 expression, particularly in BEAS-2B cells (53.0%; t = 30.993, P = 0.001) and A549 cells (42.6%; t = 14.326, P = 0.005).The miRNA-145 was up-regulated after inhibiting p-EGFR with AG1478, and significantly enhanced by 67.5% in H1975 cells when treated with AG1478 (t = 8.269, P = 0.014). The ERK1/2 signal pathway was activated by p-EGFR. U0126 restored the miRNA-145 down-regulation induced by EGFR-activation in lung cancer cells.
  
  
  CONCLUSIONS
  The activation of EGFR down-regulates miRNA-145 expression through ERK1/2 in lung cancer cells.
authors.affiliation: Department of Oncology, No. 3 People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 201900, China.
authors.forename: Yue-hui
authors.initials: YH
authors.lastname: Guo
authors.forename: Feng-hou
authors.initials: FH
authors.lastname: Gao
authors.forename: Jing
authors.initials: J
authors.lastname: Shi
authors.forename: Hai-hua
authors.initials: HH
authors.lastname: Yuan
authors.forename: Bin
authors.initials: B
authors.lastname: Jiang
mesh_terms: D002070:Butadienes / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D015536:Down-Regulation; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000166:cytology; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D020935:MAP Kinase Signaling System; D035683:MicroRNAs / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation; D011799:Quinazolines / Q000494:pharmacology; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: D002070:Butadienes; D004791:Enzyme Inhibitors; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D009570:Nitriles; D011799:Quinazolines; D020032:Tyrphostins; C113580:U 0126; C101044:RTKI cpd; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3