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MicroRNA-155 expression is independently predictive of outcome in chordoma.

AbstractBACKGROUND:
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.
AuthorsEiji Osaka, Andrew D Kelly, Dimitrios Spentzos, Edwin Choy, Xiaoqian Yang, Jacson K Shen, Pei Yang, Henry J Mankin, Francis J Hornicek, Zhenfeng Duan
JournalOncotarget (Oncotarget) Vol. 6 Issue 11 Pg. 9125-39 (Apr 20 2015) ISSN: 1949-2553 [Electronic] United States
PMID25823817 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • MIRN155 microRNA, human
  • MicroRNAs
  • RNA, Neoplasm
Topics
  • Aged
  • Aged, 80 and over
  • Cell Division
  • Cell Line, Tumor
  • Cell Movement
  • Chordoma (genetics, mortality, pathology, secondary, surgery)
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Lumbar Vertebrae
  • Male
  • MicroRNAs (antagonists & inhibitors, biosynthesis, genetics, physiology)
  • Middle Aged
  • Muscle, Skeletal (metabolism)
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Prognosis
  • RNA, Neoplasm (antagonists & inhibitors, biosynthesis, genetics, physiology)
  • Sacrum
  • Spinal Neoplasms (genetics, mortality, pathology, surgery)

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