title: Differential expression of microRNA (miRNA) in chordoma reveals a role for miRNA-1 in Met expression.
abstract: Emerging evidence suggests that microRNA (miRNA) expression signatures in cancer may have important diagnostic, prognostic, and therapeutic value, but there is no data on miRNA expression in chordoma. The purpose of this study was to identify the role of miRNAs in human chordoma. We analyzed miRNA expression in chordoma-derived cell lines and chordoma tissue by using miRNA microarray technology with unsupervised hierarchical clustering analysis. The relative expression levels of these miRNAs were confirmed by real-time quantitative RT-PCR and Northern blot analysis. To characterize the potential role of miRNA-1, miRNA-1 was stably transfected into a chordoma cell line, UCH1. The expression of miRNA-1 targeted gene Met in chordoma tissues was also studied. We observe that human chordoma tissues and cell lines can be distinguished from normal muscle tissue by comparing miRNA expression profiles. Several miRNAs were differentially expressed in chordoma cell lines compared to controls, and similar expression patterns were found in primary chordoma tissues. Importantly, we were able to show for the first time, to our knowledge, that expression of miRNA-1 and miRNA-206, two miRNAs implicated in a number of other cancer types, were markedly decreased in both chordoma tissues and cell lines. When chordoma cell lines were transfected with miRNA-1, downregulation of known miRNA-1 targets was observed. These targets included Met and HDAC4-two genes that were observed to be overexpressed in chordoma. Our results demonstrate that some miRNAs are differentially expressed in chordoma and, in particular, miRNA-1 may have a functional effect on chordoma tumor pathogenesis.
authors.affiliation: Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. zduan@partners.org
authors.forename: Zhenfeng
authors.initials: Z
authors.lastname: Duan
authors.forename: Edwin
authors.initials: E
authors.lastname: Choy
authors.forename: G Petur
authors.initials: GP
authors.lastname: Nielsen
authors.forename: Andrew
authors.initials: A
authors.lastname: Rosenberg
authors.forename: John
authors.initials: J
authors.lastname: Iafrate
authors.forename: Cao
authors.initials: C
authors.lastname: Yang
authors.forename: Joe
authors.initials: J
authors.lastname: Schwab
authors.forename: Henry
authors.initials: H
authors.lastname: Mankin
authors.forename: Ramnik
authors.initials: R
authors.lastname: Xavier
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Hornicek
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002817:Chordoma / Q000209:etiology / Q000235:genetics*; D020869:Gene Expression Profiling; D006655:Histone Deacetylases / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000032:analysis / Q000502:physiology*; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics*; D017978:Receptors, Growth Factor / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D035683:MicroRNAs; C517731:Mirn1 microRNA, mouse; D017978:Receptors, Growth Factor; D012097:Repressor Proteins; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; C400300:HDAC4 protein, human; D006655:Histone Deacetylases