title: The role of miR-18a in gastric cancer angiogenesis.
abstract: OBJECTIVE
  To investigate the effect of miR-18a on angiogenesis in gastric cancer.
  
  
  METHODS
  We generated stable cell lines overexpressing miR-18a in SGC-7901 cells. Cell proliferation was assessed by the MTT assay. The effects of miR-18a overexpression on tumor growth and angiogenesis were assessed. Because of the key role of mammalian target of rapamycin (mTOR) signaling in gastric cancer progression, we also tested whether miR-18a overexpression affected the mTOR pathway.
  
  
  RESULTS
  Ectopic expression of miR-18a significantly diminished cell proliferation in SGC-7901 cells (p<0.01). miR-18a overexpression significantly retarded SGC-7901 xenograft growth by 71.8% in vivo, and caused a marked reduction in tumor angiogenesis assessed by CD31-stained microvessel count. Western blot analysis of the xenografts showed that miR-18a overexpression substantially reduced the phosphorylation of two mTOR substrates, S6K1 and 4E-BPl, indicative of art inactivation of the mTOR pathway. Accompanying with the mTOR inactivation, the angiogenic factors, hypoxia-inducible factor 1 alpha and vascular endothelial growth factor, were significantly downregulated.
  
  
  CONCLUSIONS
  These data highlighted an important role for miR-18a in controlling gastric cancer growth and angiogenesis, therefore offering a possible therapeutic strategy against this malignancy.
authors.forename: Yongbin
authors.initials: Y
authors.lastname: Zheng
authors.forename: Shengbo
authors.initials: S
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Ding
authors.forename: Qiushuang
authors.initials: Q
authors.lastname: Wang
authors.forename: Haiping
authors.initials: H
authors.lastname: Luo
authors.forename: Qiang
authors.initials: Q
authors.lastname: Shi
authors.forename: Zhinan
authors.initials: Z
authors.lastname: Hao
authors.forename: Gaochun
authors.initials: G
authors.lastname: Xiao
authors.forename: Shilun
authors.initials: S
authors.lastname: Tong
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C522576:MIRN18A microRNA, human; D035683:MicroRNAs; D010750:Phosphoproteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C546842:MTOR protein, human; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1