title: miR-1303 targets claudin-18 gene to modulate proliferation and invasion of gastric cancer cells.
abstract: BACKGROUND
  MicroRNAs have emerged as important gene regulators and are recognized as important molecules in carcinogenesis. However, the effects of microRNA-1303 (miR-1303) on gastric cancer (GC) cells and the upstream regulation of GC-associated claudin-18 gene (CLDN18) remain unclear. miR-1303 may be involved in the tumorigenesis of GC by targeting CLDN18.
  
  
  OBJECTIVE
  The purpose of this study was to explore the effect of miR-1303 targeting of CLDN18 on the proliferation, migration and invasion of human GC cells.
  
  
  METHODS
  The expression of miR-1303 and claudin-18 in GC tissues and gastric cancer cell lines were detected by qRT-PCR and western blotting, respectively. CCK8 and colony formation assays were performed to study the influence of miR-1303 on the proliferation of the GC cell lines. Transwell and wound-healing assays were carried out to investigate the effect of miR-1303 on the invasion and migration of GC cell lines. Luciferase reporter assays, restore assays and western blotting were used to demonstrate whether CLDN18 is a direct target of miR-1303.
  
  
  RESULTS
  miR-1303 was significantly overexpressed whereas claudin-18 was downregulated in GC tissues and cell lines, which was significantly associated with tumor size, location invasion, histologic type and tumor-node-metastasis stage. Cell proliferation rates were reduced, and cell invasion and migratory ability was significantly restricted in miR-1303 inhibitor-transfected groups. miR-1303 could bind to the putative binding sites in CLDN18 mRNA 3'-UTR and visibly lower the expression of claudin-18. The introduction of claudin-18 without 3'-UTR restored the miR-1303 promoting migration function.
  
  
  CONCLUSIONS
  Downregulation of miR-1303 can inhibit proliferation, migration and invasion of GC cells by targeting CLDN18.
authors.affiliation: Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China, zsj03@zzu.edu.cn.
authors.forename: Shi-jie
authors.initials: SJ
authors.lastname: Zhang
authors.forename: Jian-fang
authors.initials: JF
authors.lastname: Feng
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.forename: Yu-wen
authors.initials: YW
authors.lastname: Du
authors.forename: Liang
authors.initials: L
authors.lastname: Ming
authors.forename: Guo-qiang
authors.initials: GQ
authors.lastname: Zhao
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D057167:Claudins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009361:Neoplasm Invasiveness; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: C486683:CLDN18 protein, human; D057167:Claudins; C000592164:MIRN1303 microRNA, human; D035683:MicroRNAs