title: MicroRNA-206 expression levels correlate with clinical behaviour of rhabdomyosarcomas.
abstract: BACKGROUND
  Rhabdomyosarcomas (RMSs) are primarily paediatric sarcomas that resemble developing skeletal muscle. Our aim was to determine the effects of microRNAs (miRNA) that have been implicated in muscle development on the clinical behaviour of RMSs.
  
  
  METHODS
  Expression levels of miR-1, miR-206, miR-133a and miR-133b were quantified by RT-PCR in 163 primary paediatric RMSs, plus control tissues, and correlated with clinico-pathological features. Correlations with parallel gene expression profiling data for 84 samples were used to identify pathways associated with miR-206. Synthetic miR-206 was transfected into RMS cell lines and phenotypic responses assessed.
  
  
  RESULTS
  Muscle-specific miRNAs levels were lower in RMSs compared with skeletal muscle but generally higher than in other normal tissues. Low miR-206 expression correlated with poor overall survival and was an independent predictor of shorter survival in metastatic embryonal and alveolar cases without PAX3/7-FOXO1 fusion genes. Low miR-206 expression also significantly correlated with high SIOP stage and the presence of metastases at diagnosis. High miR-206 expression strongly correlated with genes linked to muscle differentiation and low expression was associated with genes linked to MAPkinase and NFKappaB pathway activation. Increasing miR-206 expression in cell lines inhibited cell growth and migration and induced apoptosis that was associated with myogenic differentiation in some, but not all, cell lines.
  
  
  CONCLUSIONS
  miR-206 contributes to the clinical behaviour of RMSs and the pleiotropic effects of miR-206 supports therapeutic potential.
authors.affiliation: Molecular Cytogenetics Team, The Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
authors.forename: E
authors.initials: E
authors.lastname: Missiaglia
authors.forename: C J
authors.initials: CJ
authors.lastname: Shepherd
authors.forename: S
authors.initials: S
authors.lastname: Patel
authors.forename: K
authors.initials: K
authors.lastname: Thway
authors.forename: G
authors.initials: G
authors.lastname: Pierron
authors.forename: K
authors.initials: K
authors.lastname: Pritchard-Jones
authors.forename: M
authors.initials: M
authors.lastname: Renard
authors.forename: R
authors.initials: R
authors.lastname: Sciot
authors.forename: P
authors.initials: P
authors.lastname: Rao
authors.forename: O
authors.initials: O
authors.lastname: Oberlin
authors.forename: O
authors.initials: O
authors.lastname: Delattre
authors.forename: J
authors.initials: J
authors.lastname: Shipley
mesh_terms: D000293:Adolescent; D000328:Adult; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007223:Infant; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D012208:Rhabdomyosarcoma / Q000235:genetics* / Q000401:mortality; D014162:Transfection; D025521:Tumor Suppressor Proteins
chemical_list: C546087:MIRN206 microRNA, human; D035683:MicroRNAs; D025521:Tumor Suppressor Proteins