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Gastrokine 1 inhibits gastric cancer cell migration and invasion by downregulating RhoA expression
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Gastrokine 1 inhibits gastric cancer cell migration and invasion by downregulating RhoA expression
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Journal Article
Gastrokine 1 inhibits gastric cancer cell migration and invasion by downregulating RhoA expression
2017
Overview
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.
Conclusion
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.
Publisher
Springer Japan,Springer Nature B.V
Subject
/ Biobanks
/ Biomarkers, Tumor - genetics
/ Biomarkers, Tumor - metabolism
/ Epithelial-Mesenchymal Transition
/ Gene Expression Regulation, Neoplastic
/ Humans
/ Kinases
/ Medicine
/ Motility
/ Mutation
/ Oncology
/ Peptide Hormones - pharmacology
/ Real-Time Polymerase Chain Reaction
/ Reverse Transcriptase Polymerase Chain Reaction
/ rhoA GTP-Binding Protein - antagonists & inhibitors
/ rhoA GTP-Binding Protein - genetics
/ rhoA GTP-Binding Protein - metabolism
/ siRNA
/ Stomach Neoplasms - genetics
/ Stomach Neoplasms - metabolism
/ Stomach Neoplasms - pathology
/ Vimentin
