MicroRNA-155 expression is independently predictive of outcome in chordoma
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Eiji Osaka1,2, Andrew D. Kelly3, Dimitrios Spentzos4, Edwin Choy1, Xiaoqian Yang1, Jacson K. Shen1, Pei Yang1, Henry J. Mankin1, Francis J. Hornicek1, Zhenfeng Duan1
1Sarcoma Biology Laboratory, Department of Orthopaedic Surgery, Massachusetts General Hospital, Boston, MA 02114, USA
2Department of Orthopaedic Surgery, Nihon University School of Medicine, Tokyo 173–8610, Japan
3Fels Institute for Cancer Research & Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA
4Division of Hematology/Oncology, Sarcoma Program, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
Zhenfeng Duan, e-mail: firstname.lastname@example.org
Keywords: miRNA-155 (miR-155), chordoma, prognosis, miRNA microarray assay, RT-PCR
Received: November 19, 2014 Accepted: February 07, 2015 Published: March 16, 2015
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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