Differential expression of microRNA (miRNA) in chordoma reveals a role for miRNA-1 in met expression

Zhenfeng Duan, Edwin Choy, G. Petur Nielsen, Andrew Rosenberg, John Iafrate, Cao Yang, Joe Schwab, Henry Mankin, Ramnik Xavier, Francis J. Hornicek

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

Emerging evidence suggests that microRNA (miRNA) expression signatures in cancer may have important diagnostic, prognostic, and therapeutic value, but there is no data onmiRNAexpression 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 Metin 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.

Original languageEnglish (US)
Pages (from-to)746-752
Number of pages7
JournalJournal of Orthopaedic Research
Volume28
Issue number6
DOIs
StatePublished - Jun 1 2010

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Keywords

  • Chordoma
  • Met
  • miRNA
  • RT-PCR

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

Cite this

Duan, Z., Choy, E., Petur Nielsen, G., Rosenberg, A., Iafrate, J., Yang, C., Schwab, J., Mankin, H., Xavier, R., & Hornicek, F. J. (2010). Differential expression of microRNA (miRNA) in chordoma reveals a role for miRNA-1 in met expression. Journal of Orthopaedic Research, 28(6), 746-752. https://doi.org/10.1002/jor.21055