title: Ginkgolide B Inhibits Human Bladder Cancer Cell Migration and Invasion Through MicroRNA-223-3p.
abstract: OBJECTIVE
  Ginkgolide B (GB) is currently used as an anticancer drug for treatment of some malignant cancers. However, whether it may have therapeutic effects on bladder cancer remains unknown. Here, we studied the effects of GB on bladder cancer cells.
  
  
  METHODS
  Bladder cells were treated with different doses of GB, and the effects on ZEB1 and microRNA-223-3p (miR-223-3p) were analyzed by RT-qPCR and/or Western blot. Prediction of a regulatory relationship between miR-93 and 3'-UTR of Beclin-1 mRNA was performed by a bioinformatics algorithm and confirmed by a dual luciferase reporter assay.
  
  
  RESULTS
  We found that GB dose-dependently decreased ZEB1 protein, but not mRNA, in bladder cancer cells, resulting in suppression of cell invasion. Moreover, in bladder cancer cells, GB dose-dependently decreased the levels of miR-223-3p, which suppressed the protein translation of ZEB1 through binding to 3'-UTR of ZEB1 mRNA. Overexpression of miR-223-3p decreased ZEB1 protein, while depletion of miR-223-3p increased ZEB1 protein in bladder cancer cells.
  
  
  CONCLUSIONS
  GB inhibits bladder cancer cell invasiveness through suppressing ZEB1 protein translation via upregulating miR-223-3p.
authors.affiliation: Urology Institute of People Liberation Army, Southwest Hospital, the Third Military Medical University, Chongqing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhi
authors.forename: Jinhong
authors.initials: J
authors.lastname: Pan
authors.forename: Wenhao
authors.initials: W
authors.lastname: Shen
authors.forename: Peng
authors.initials: P
authors.lastname: He
authors.forename: Ji
authors.initials: J
authors.lastname: Zheng
authors.forename: Xiaozhou
authors.initials: X
authors.lastname: Zhou
authors.forename: Gensheng
authors.initials: G
authors.lastname: Lu
authors.forename: Zhiwen
authors.initials: Z
authors.lastname: Chen
authors.forename: Zhansong
authors.initials: Z
authors.lastname: Zhou
mesh_terms: D020413:3' Untranslated Regions; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D000071186:Beclin-1 / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D046934:Ginkgolides / Q000494:pharmacology*; D006801:Humans; D007783:Lactones / Q000494:pharmacology*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D014176:Protein Biosynthesis; D015398:Signal Transduction; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000071799:Zinc Finger E-box-Binding Homeobox 1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D000972:Antineoplastic Agents, Phytogenic; D000071186:Beclin-1; D046934:Ginkgolides; D007783:Lactones; D008156:Luciferases; D035683:MicroRNAs; D000071799:Zinc Finger E-box-Binding Homeobox 1; C491997:BECN1 protein, human; C525067:MIR223, human; C486307:ZEB1 protein, human; C045856:ginkgolide B