title: miR-454 is down-regulated in osteosarcomas and suppresses cell proliferation and invasion by directly targeting c-Met.
abstract: OBJECTIVE
  Osteosarcoma is the most common primary bone malignancy of children and young adults. Increasing evidence has shown that microRNAs (miRNAs) are associated with cancer development, but, little is known concerning the role of miR-454 in osteosarcoma.
  
  
  METHODS
  qRT-PCR was performed to detect expression of miR-454 in osteosarcoma cell lines and tissues. To understand its role in osteosarcoma, we reintroduced expression of miR-454 in the MG-63 cell line by transfection with miR-454 mimics or inhibitors. CCK-8 assay and an invasion assay were used to detect the functional role of miR-454. Luciferase assay and western blot analysis were performed to detect the target gene of miR-454.
  
  
  RESULTS
  miR-454 was found to be down-regulated in osteosarcoma tissues and cell lines. Its over-expression inhibited tumour growth and invasion and its down-regulation promoted cell proliferation and invasion. Subsequent investigation revealed that c-Met was a direct and functional target of miR-454 in osteosarcoma. Overexpression of miR-454 impaired c-Met-induced cell proliferation and invasion. Finally, miR-454 was found to be inversely correlated to c-Met expression in human osteosarcoma tissues.
  
  
  CONCLUSIONS
  Reduced-expression of miR-454 in osteosarcoma cells promoted tumour growth by targeting c-Met, thus miR-454 may be a potential therapy target for this tumour.
authors.affiliation: Department of Orthopaedics, Shandong Provincial Hospital affiliated to Shandong University, Jinan, 250021, China.
authors.forename: Guangfeng
authors.initials: G
authors.lastname: Niu
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.forename: Jianmin
authors.initials: J
authors.lastname: Sun
authors.forename: Li
authors.initials: L
authors.lastname: Sun
mesh_terms: D000328:Adult; D001665:Binding Sites; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002648:Child; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D012516:Osteosarcoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection
chemical_list: C583712:MIRN454 microRNA, human; D035683:MicroRNAs; D008156:Luciferases; D019859:Proto-Oncogene Proteins c-met