Differential expression of microRNA (miRNA) in chordoma reveals a role for miRNA-1 in Met expression.
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.
Duan
Zhenfeng
Z
Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. zduan@partners.org
Choy
Edwin
E
Nielsen
G Petur
GP
Rosenberg
Andrew
A
Iafrate
John
J
Yang
Cao
C
Schwab
Joe
J
Mankin
Henry
H
Xavier
Ramnik
R
Hornicek
Francis J
FJ
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
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