title: miR-138 inhibits proliferation by targeting 3-phosphoinositide-dependent protein kinase-1 in non-small cell lung cancer cells.
abstract: OBJECTIVE
  Underlying mechanisms of non-small cell lung cancer (NSCLC) development remain poorly understood. miR-138 and 3-phosphoinositide-dependent protein kinase-1 (PDK1) have been reported to be involved in the genesis of NSCLC. The aim of this study was to investigate the role and mechanisms of miR-138 and PDK1 in human NSCLC cells.
  
  
  METHODS
  The effect of miR-138 on proliferation of A549 lung cancer cells was first examined using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay. The expression of PDK1 in A549 lung cancer cells was assessed by real-time polymerase chain reaction further. A luciferase reporter activity assay was conducted to confirm target association between miR-138 and 3' untranslated region (3'-UTR) of PDK1. Finally, the role of PDK1 on proliferation of A549 cells was evaluated by transefection of PDK1 small interfering RNA (siRNA).
  
  
  RESULTS
  Proliferation of A549 lung cancer cells was suppressed by miR-138 in a concentration-dependent manner. Furthermore, miR-138 can bind to the 3'-UTR of PDK1 and downregulate expression of PDK1 at both mRNA and protein levels. Knockdown of PDK1 by siRNA significantly inhibits the proliferation of A549 lung cancer cells.
  
  
  CONCLUSIONS
  These findings suggest that miR-138 as a potential tumor suppressor could inhibit cell proliferation by targeting PDK1 in NSCLC cells, which could be employed as a potential therapeutic target for miRNA-based NSCLC therapy.
authors.affiliation: Department of Respiratory Medicine, The People's Hospital of Guizhou Province, Guiyang, China; Academic Department, Guizhou Institute of Respiratory Diseases, Guiyang, China.
authors.forename: Xian-wei
authors.initials: XW
authors.lastname: Ye
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
authors.forename: Yan-kun
authors.initials: YK
authors.lastname: Jin
authors.forename: Xiao-ting
authors.initials: XT
authors.lastname: Jing
authors.forename: Mei
authors.initials: M
authors.lastname: Xu
authors.forename: Zi-fen
authors.initials: ZF
authors.lastname: Wan
authors.forename: Xiang-yan
authors.initials: XY
authors.lastname: Zhang
mesh_terms: D064413:3-Phosphoinositide-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000209:etiology / Q000473:pathology*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000209:etiology / Q000473:pathology*; D035683:MicroRNAs / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: C546110:MIRN138 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D064413:3-Phosphoinositide-Dependent Protein Kinases
keywords: 3-phosphoinositide-dependent protein kinase-1; cell proliferation; miR-138; non-small cell lung cancer; siRNA