title: The miR-506-Induced Epithelial-Mesenchymal Transition is Involved in Poor Prognosis for Patients with Gastric Cancer.
abstract: BACKGROUND
  MicroRNAs have roles in the regulation of the epithelial-mesenchymal transition (EMT). Findings have shown that miR-506 inhibits the expression of SNAI2 and that low expression of miR-506 is associated with poor prognoses in ovarian and breast cancers. This study investigated the role of miR-506 in survival and the EMT in patients with gastric cancer.
  
  
  METHODS
  In this study, miR-506 and SNAI2 mRNA levels were measured in 141 cases of gastric cancer by quantitative reverse transcription polymerase chain reaction, and the protein expressions of SNAI2 and E-cadherin in 39 cases were validated by immunohistochemical analysis. Next, the associations between their expression levels and clinicopathologic factors were evaluated. In addition, cell proliferation, migration, and luciferase activity of the 3' untranslated region (UTR) of SNAI2 were analyzed using pre-miR-506 precursor in two human gastric cancer cell lines.
  
  
  RESULTS
  Low expression of miR-506 was significantly correlated with poor overall survival in both the univariate analysis (P = 0.016) and the multivariate analysis (P < 0.05). Low miR-506 expression was significantly correlated with high SNAI2 expression (P = 0.009) and poorly differentiated type (P = 0.015). In vitro, miR-506 suppressed SNAI2 expression by binding to its 3'UTR, resulting in increased expression of E-cadherin (P < 0.05), verified by immunohistochemical analysis. Pre-miR-506 transfected cells showed significantly suppressed cell proliferation and migration (P < 0.05) compared with the control cells.
  
  
  CONCLUSIONS
  The EMT was directly suppressed by miR-506, and its low expression was an independent prognostic factor in gastric cancer patients. The data indicated that miR-506 may act as a tumor suppressor and could be a novel therapeutic agent.
authors.affiliation: Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.|Department of Anesthesiology and Critical Care Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Shotaro
authors.initials: S
authors.lastname: Sakimura
authors.affiliation: Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.
authors.forename: Keishi
authors.initials: K
authors.lastname: Sugimachi
authors.affiliation: Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Kurashige
authors.affiliation: Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Ueda
authors.affiliation: Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.
authors.forename: Hidenari
authors.initials: H
authors.lastname: Hirata
authors.affiliation: Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Nambara
authors.affiliation: Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.
authors.forename: Hisateru
authors.initials: H
authors.lastname: Komatsu
authors.affiliation: Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Saito
authors.affiliation: Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Takano
authors.affiliation: Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Uchi
authors.affiliation: Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.
authors.forename: Etsuko
authors.initials: E
authors.lastname: Sakimura
authors.affiliation: Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Shinden
authors.affiliation: Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Iguchi
authors.affiliation: Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Eguchi
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Yugo
authors.initials: Y
authors.lastname: Oba
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Sumio
authors.initials: S
authors.lastname: Hoka
authors.affiliation: Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan. kmimori@beppu.kyushu-u.ac.jp.
authors.forename: Koshi
authors.initials: K
authors.lastname: Mimori
mesh_terms: D000368:Aged; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D002465:Cell Movement; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071250:Snail Family Transcription Factors; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology*; D015996:Survival Rate; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; C561508:MIRN506 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C000604408:SNAI2 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors