title: Gastrokine 1 inhibits gastric cancer cell migration and invasion by downregulating RhoA expression.
abstract: BACKGROUND
  We investigated whether GKN1, a gastric tumor suppressor, contributes to the progression of gastric cancer by regulating RhoA expression.
  
  
  METHODS
  We analyzed the expression of GKN1, RhoA, miR-185, and miR-34a in 35 gastric cancer tissues, and compared their expression with T category and TNM stage. Cell migration and invasion, as well as the expression of epithelial-to-mesenchymal transition (EMT)-related proteins, were assessed in GKN1- and RhoA small interfering RNA (siRhoA)-transfected and recombinant-GKN1-treated AGS and MKN1 gastric cancer cells.
  
  
  RESULTS
  Expression of RhoA protein and messenger RNA (mRNA) was increased in 15 (42.9 %) and 17 (48.6 %) of 35 gastric cancer tissues respectively, and was associated with higher T category and TNM stage. GKN1 expression was significantly decreased in 27 gastric cancers (77.1 %) with a higher T category, and was inversely correlated with RhoA mRNA expression. In AGS and MKN1 cells, GKN1 expression increased miR-185 and miR-34a expression and reduced RhoA mRNA and protein expression. A positive relationship between GKN1 and miR-34a and miR-185 expression and an inverse relationship between miR-34a and RhoA expression were observed in gastric cancer tissues. Cell migration and invasiveness were markedly decreased in GKN1- and siRhoA-transfected cells. GKN1 expression and silencing of RhoA decreased the expression of the proteins Snail, Slug, and vimentin. Furthermore, miR-185 and miR-34a silencing in MKN1 cells transfected with GKN1 stimulated cell migration and invasion, and increased the expression of EMT-related proteins.
  
  
  CONCLUSIONS
  Our data suggest that GKN1 may inhibit gastric cancer cell migration and invasion by downregulating RhoA expression in a miR-185- and miR-34a-dependent manner.
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul, 137-701, Korea.
authors.forename: Jung Hwan
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul, 137-701, Korea.
authors.forename: Won Suk
authors.initials: WS
authors.lastname: Choi
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul, 137-701, Korea.
authors.forename: Olga
authors.initials: O
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul, 137-701, Korea.
authors.forename: Byung Joon
authors.initials: BJ
authors.lastname: Choi
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul, 137-701, Korea.
authors.forename: Suk Woo
authors.initials: SW
authors.lastname: Nam
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul, 137-701, Korea.
authors.forename: Jung Young
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul, 137-701, Korea. wonsang@catholic.ac.kr.
authors.forename: Won Sang
authors.initials: WS
authors.lastname: Park
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D036361:Peptide Hormones / Q000494:pharmacology*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C477000:GKN1 protein, human; C552431:MIRN185 microRNA, human; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D036361:Peptide Hormones; D012333:RNA, Messenger; C066737:RHOA protein, human; D020742:rhoA GTP-Binding Protein
keywords: Gastric cancer; Gastrokine 1; Invasion; RhoA; miR-185