title: POU2F2-oriented network promotes human gastric cancer metastasis.
abstract: Aberrant upregulation of POU2F2 expression has been discovered in metastatic gastric cancer (GC). However, the mechanisms underlying the aberrant upregulation and the potential functions of POU2F2 remain uncertain.
  
  
  
  The role and mechanism of POU2F2 in GC metastasis were investigated in gastric epithelial cells, GC cell lines and an experimental metastasis animal model by gain of function and loss of function. Upstream and downstream targets of POU2F2 were selected by bioinformatics and identified by luciferase reporter assay, electrophoretic mobility shift assay and chromatin immunoprecipitation PCR. The influence of miR-218 on its putative target genes (POU2F2, ROBO1 and IKK-β) and GC metastasis was further explored via in vitro and in vivo approaches.
  
  
  
  Increased POU2F2 expression was detected in metastatic GC cell lines and patient samples. POU2F2 was induced by the activation of nuclear factor (NF)-κB and, in turn, regulated ROBO1 transcription, thus functionally contributing to GC metastasis. Finally, miR-218 was found to suppress GC metastasis by simultaneously mediating multiple molecules in the POU2F2-oriented network.
  
  
  
  This study demonstrated that NF-κB and the SLIT2/ROBO1 interaction network with POU2F2 as the central part may exert critical effects on tumour metastasis. Blocking the activation of the POU2F2-oriented metastasis network using miR-218 precursors exemplified a promising approach that sheds light on new strategies for GC treatment.
authors.affiliation: State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Si-Meng
authors.initials: SM
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Tie
authors.affiliation: Department of Aerospace Hygiene and Health Service, School of Aerospace Medicine, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Wen-Lan
authors.initials: WL
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Si-Jun
authors.initials: SJ
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Ji-Peng
authors.initials: JP
authors.lastname: Yin
authors.affiliation: State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Yi
authors.affiliation: State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Zu-Hong
authors.initials: ZH
authors.lastname: Tian
authors.affiliation: State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Xiang-Yuan
authors.initials: XY
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Meng-Bin
authors.initials: MB
authors.lastname: Li
authors.affiliation: Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Zeng-Shan
authors.initials: ZS
authors.lastname: Li
authors.affiliation: State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Yong-Zhan
authors.initials: YZ
authors.lastname: Nie
authors.affiliation: State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Kai-Chun
authors.initials: KC
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Dai-Ming
authors.initials: DM
authors.lastname: Fan
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009362:Neoplasm Metastasis / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D050813:Octamer Transcription Factor-2 / Q000235:genetics*; D011971:Receptors, Immunologic / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D035683:MicroRNAs; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D050813:Octamer Transcription Factor-2; D011971:Receptors, Immunologic; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein; C547471:MIRN218 microRNA, human; C058435:POU2F2 protein, human
keywords: CANCER GENETICS; CELL MIGRATION; CELL SIGNALLING; GASTROINTESTINAL CANCER; ONCOGENES