MicroRNA-155 Expression Is Independently Predictive of Outcome in Chordoma

Oncotarget. 2015 Apr 20;6(11):9125-39. doi: 10.18632/oncotarget.3273.

Abstract

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.

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

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cell Division
  • Cell Line, Tumor
  • Cell Movement
  • Chordoma / genetics*
  • Chordoma / mortality
  • Chordoma / pathology
  • Chordoma / secondary
  • Chordoma / surgery
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Lumbar Vertebrae
  • Male
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics
  • MicroRNAs / physiology*
  • Middle Aged
  • Muscle, Skeletal / metabolism
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Prognosis
  • RNA, Neoplasm / antagonists & inhibitors
  • RNA, Neoplasm / biosynthesis
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / physiology*
  • Sacrum
  • Spinal Neoplasms / genetics*
  • Spinal Neoplasms / mortality
  • Spinal Neoplasms / pathology
  • Spinal Neoplasms / surgery

Substances

  • MIRN155 microRNA, human
  • MicroRNAs
  • RNA, Neoplasm