4.3 Article

MicroRNA-155 expression is independently predictive of outcome in chordoma

Journal

ONCOTARGET
Volume 6, Issue 11, Pages 9125-9139

Publisher

IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.3273

Keywords

miRNA-155 (miR-155); chordoma; prognosis; miRNA microarray assay; RT-PCR

Funding

  1. Stephan L. Harris Fund
  2. Chordoma Foundation
  3. Sarcoma Foundation of America (SFA)
  4. National Cancer Institute (NCI)/National Institutes of Health (NIH) [CA151452-01]
  5. Sarcoma SPORE/NIH
  6. Academic Enrichment Fund of MGH Orthopedic Surgery
  7. Gattegno fund
  8. Wechsler fund

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Background: Chordoma pathogenesis remains poorly understood. In this study, we aimed to evaluate the relationships between microRNA-155 (miR-155) expression and the clinicopathological features of chordoma patients, and to evaluate the functional role of miR-155 in chordoma. Methods: The miRNA expression profiles were analyzed using miRNA microarray assays. Regulatory activity of miR-155 was assessed using bioinformatic tools. miR-155 expression levels were validated by reverse transcription-polymerase chain reaction. The relationships between miR-155 expression and the clinicopathological features of chordoma patients were analyzed. Proliferative, migratory and invasive activities were assessed by MTT, wound healing, and Matrigel invasion assays, respectively. Results: The miRNA microarray assay revealed miR-155 to be highly expressed and biologically active in chordoma. miR-155 expression in chordoma tissues was significantly elevated, and this expression correlated significantly with disease stage (p = 0.036) and the presence of metastasis (p = 0.035). miR-155 expression also correlated significantly with poor outcomes for chordoma patients (hazard ratio, 5.32; p = 0.045). Inhibition of miR-155 expression suppressed proliferation, and the migratory and invasive activities of chordoma cells. Conclusions: We have shown miR-155 expression to independently affect prognosis in chordoma. These results collectively indicate that miR-155 expression may serve not only as a prognostic marker, but also as a potential therapeutic target in chordoma.

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