title: TGF-β1 promotes osteosarcoma cell migration and invasion through the miR-143-versican pathway.
abstract: OBJECTIVE
  TGF-β1 is an abundant cytokine present in the tumour microenvironment. It has been shown to trigger versican expression in human osteosarcoma cells, which may account for the metastatic potential of these cells. However, the underlying mechanism of TGF-β1-mediated metastasis remains unclear. The aim of this study was to evaluate the roles of versican in TGF-β1-induced osteosarcoma cell migration and invasion.
  
  
  METHODS
  Sixty paired osteosarcoma tumour tissues and adjacent normal tissues were obtained, and the relationship between Enneking stage and versican expression was tested by ANOVA analysis. Real-time PCR or Western blot was used to detect versican, Smad and miR-143 expression. Osteosarcoma cell migration and invasion was assessed using Boyden chambers. A luciferase reporter assay was employed to validate the miR-143-versican interaction.
  
  
  RESULTS
  Both versican isoforms, V0 and V1, were significantly differentially expressed in tumours at different stages. TGF-β1 promoted osteosarcoma cell migration and invasion in vitro by up-regulating versican. Furthermore, TGF-β1 suppressed miR-143 expression through a Smad 2/3-dependent pathway. miR-143 directly targets the versican 3'-UTR, and anti-miR-143 or versican knockdown blocked the effects of TGF-β1.
  
  
  CONCLUSIONS
  Our results suggest that TGF-β1 up-regulates versican expression by suppressing miR-143, and this pathway is important for osteosarcoma cell migration and invasion.
authors.affiliation: Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Fengfeng
authors.initials: F
authors.lastname: Li
authors.forename: Shaohua
authors.initials: S
authors.lastname: Li
authors.forename: Tao
authors.initials: T
authors.lastname: Cheng
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics; D012516:Osteosarcoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000008:administration & dosage / Q000378:metabolism*; D059016:Tumor Microenvironment / Q000235:genetics; D053675:Versicans / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C542359:MIRN143 microRNA, human; D035683:MicroRNAs; D053773:Transforming Growth Factor beta1; D053675:Versicans