title: Modulation of the osteosarcoma expression phenotype by microRNAs.
abstract: BACKGROUND
  Osteosarcomas are the most common primary malignant tumors of bone and show multiple and complex genomic aberrations. miRNAs are non-coding RNAs capable of regulating gene expression at the post transcriptional level, and miRNAs and their target genes may represent novel therapeutic targets or biomarkers for osteosarcoma. In order to investigate the involvement of miRNAs in osteosarcoma development, global microarray analyses of a panel of 19 human osteosarcoma cell lines was performed.
  
  
  RESULTS
  We identified 177 miRNAs that were differentially expressed in osteosarcoma cell lines relative to normal bone. Among these, miR-126/miR-126*, miR-142-3p, miR-150, miR-223, miR-486-5p and members of the miR-1/miR-133a, miR-144/miR-451, miR-195/miR-497 and miR-206/miR-133b clusters were found to be downregulated in osteosarcoma cell lines. All miRNAs in the paralogous clusters miR-17-92, miR-106b-25 and miR-106a-92 were overexpressed. Furthermore, the upregulated miRNAs included miR-9/miR-9*, miR-21*, miR-31/miR-31*, miR-196a/miR-196b, miR-374a and members of the miR-29 and miR-130/301 families. The most interesting inversely correlated miRNA/mRNA pairs in osteosarcoma cell lines included miR-9/TGFBR2 and miR-29/p85α regulatory subunit of PI3K. PTEN mRNA correlated inversely with miR-92a and members of the miR-17 and miR-130/301 families. Expression profiles of selected miRNAs were confirmed in clinical samples. A set of miRNAs, miR-1, miR-18a, miR-18b, miR-19b, miR-31, miR-126, miR-142-3p, miR-133b, miR-144, miR-195, miR-223, miR-451 and miR-497 was identified with an intermediate expression level in osteosarcoma clinical samples compared to osteoblasts and bone, which may reflect the differentiation level of osteosarcoma relative to the undifferentiated osteoblast and fully differentiated normal bone.
  
  
  CONCLUSIONS
  This study provides an integrated analysis of miRNA and mRNA in osteosarcoma, and gives new insight into the complex genetic mechanisms of osteosarcoma development and progression.
authors.affiliation: The EuroBoNet Network of Excellence on Bone Tumours, Department of Tumor Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors.forename: Heidi M
authors.initials: HM
authors.lastname: Namløs
authors.forename: Leonardo A
authors.initials: LA
authors.lastname: Meza-Zepeda
authors.forename: Tale
authors.initials: T
authors.lastname: Barøy
authors.forename: Ingrid H G
authors.initials: IH
authors.lastname: Østensen
authors.forename: Stine H
authors.initials: SH
authors.lastname: Kresse
authors.forename: Marieke L
authors.initials: ML
authors.lastname: Kuijjer
authors.forename: Massimo
authors.initials: M
authors.lastname: Serra
authors.forename: Horst
authors.initials: H
authors.lastname: Bürger
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Cleton-Jansen
authors.forename: Ola
authors.initials: O
authors.lastname: Myklebost
mesh_terms: D014408:Biomarkers, Tumor; D001859:Bone Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D012516:Osteosarcoma / Q000378:metabolism*; D010641:Phenotype; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D012333:RNA, Messenger; D012313:RNA