title: microRNA-203 suppresses invasion of gastric cancer cells by targeting ERK1/2/Slug/ E-cadherin signaling.
abstract: OBJECTIVE
  Growing evidence suggests that microRNA plays an essential role in the development and metastasis of many tumors, including gastric cancer (GC). Expression of microRNA-203 (miR-203) has been reported to decrease in GC. In addition, overexpression of miR-203 inhibits grow of GC cells in vitro and in vivo. However, whether miR-203 affects cell migration and invasion of GC remains unclear. This study aimed to reveal the role of miR-203 on migration and invasion of GC, and its potential mechanisms.
  
  
  METHODS
  Synthetic pre-miR-203 (miR-203), anti-miR-203 and scrambled negative control RNAs was transfected into the gastric cancer SGC7901 cells to generate miR-203 or anti-miR-203-transfected stable clones. The roles of miR-203 on cell invasion and motility were then analyzed by Transwell migration assay and Wound healing assay in vitro. Using siRNA to targeting ERK1/2, Slug, and E-cadherin or Slug cDNA transfection (to increase Slug expression) to examine the miR-203 signaling pathway. We also examined the efficacies of miR-203 or anti-miR-203 on peritoneal metastasis of SGC7901 cells in the nude mouse model.
  
  
  RESULTS
  Overexpression of miR-203 inhibits SGC7901 cell invasion and motility, followed by decreased phospho-ERK1/2 (pERK1/2) and Slug expression, as well as increased E-cadherin expression. Re-expression of Slug in miR-203/SGC7901cells decreased E-cadherin expression and restored the invasive phenotypes. Targeting E-cadherin in miR-203/SGC7901cells also restored the invasive phenotypes. Inhibition of miR-203 promotes SGC7901 cell invasion and motility, followed by increased phospho-ERK1/2 (pERK1/2) and Slug expression, as well as decreased E-cadherin expression. Targeting ERK1/2 or Slug in anti-miR-203/SGC7901cells increased E-cadherin expression and reversed the invasive phenotypes. In addition, targeting ERK1/2 decreased Slug and increased the E-cadherin expression. Significantly, we found that miR-203 could exert marked inhibition of the peritoneal metastasis of SGC7901 in nude mice in vivo. Targeting miR-203 could exert marked promotion of the peritoneal metastasis of SGC7901 in nude mice in vivo.
  
  
  CONCLUSIONS
  miR-203/ERK1/2/Slug/E-cadherin signaling pathway plays an essential role on SGC7901 cell invasion and motility. miR-203 can be novel modalities to prevent peritoneal metastasis of invasive cancers such as gastric cancer.
authors.affiliation: Department of Emergency Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Gao
authors.affiliation: Department of Gastroenterology, People's Hospital of Juxian, Rizhao, Shandong, China.
authors.forename: Shijie
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
authors.forename: Fuchun
authors.initials: F
authors.lastname: Jing
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhan
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
authors.forename: Yunhui
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics; D015820:Cadherins / Q000235:genetics*; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics; D010534:Peritoneal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D015398:Signal Transduction / Q000235:genetics; D000071250:Snail Family Transcription Factors / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; C546703:MIRN203 microRNA, human; D035683:MicroRNAs; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors
keywords: Gastric cancer; extracellular signal-regulated kinase (ERK); invasion; microRNA-203; slug