MiR-495 is a Predictive Biomarker that Downregulates GFI1 Expression in Medulloblastoma

Cell Physiol Biochem. 2015;36(4):1430-9. doi: 10.1159/000430308.

Abstract

Background: Alterations in the expression level of miR-495 were recently observed in various tumours. Medulloblastoma is the most common malignant brain tumour in children. However, the clinical significance of miR-495 in medulloblastomas remains unclear.

Methods: The expression levels of miR-495 was examined in 62 archival formalin-fixed paraffin-embedded (FFPE) medulloblastoma specimens using TaqMan Real-time Quantitative PCR arrays. Immunohistochemistry was used to determine the expression of Gfi1 in medulloblastoma tissues, and a luciferase reporter assay was carried out to confirm whether Gfi1 is a direct target of miR-495.

Results: MiR-495 expression is repressed in medulloblastoma samples compared with normal cerebellum tissues. Furthermore, patients with a low level of miR- 495 showed significantly poorer survival, as determined by the log-rank test (P = 0.033). The multivariate analysis results showed that the miR-495 expression levels were an independent predictor of overall survival in medulloblastoma patients (P = 0.027; hazard ratio = 0.267). Our study provides the first demonstration that miR-495 directly interacts with the Gfi1 3’UTR to regulate Gfi1 at a post-transcriptional level and that the expression level of miR-495 is inversely correlated with the Gfi1 protein level in medulloblastoma specimens.

Conclusion: Our results suggest that miR-495 may be a prognostic predictor in medulloblastoma and that Gfi1 is a potential functional target of miR-495.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Base Sequence
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics
  • Cell Line, Tumor
  • Cerebellar Neoplasms / diagnosis
  • Cerebellar Neoplasms / genetics*
  • Cerebellar Neoplasms / pathology
  • Cerebellum / metabolism
  • Cerebellum / pathology*
  • Child
  • Child, Preschool
  • DNA-Binding Proteins / analysis
  • DNA-Binding Proteins / genetics*
  • Down-Regulation*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Infant
  • Male
  • Medulloblastoma / diagnosis
  • Medulloblastoma / genetics*
  • Medulloblastoma / pathology
  • MicroRNAs / analysis
  • MicroRNAs / genetics*
  • Middle Aged
  • Prognosis
  • Real-Time Polymerase Chain Reaction
  • Survival Analysis
  • Transcription Factors / analysis
  • Transcription Factors / genetics*
  • Young Adult

Substances

  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • GFI1 protein, human
  • MIRN495 microRNA, human
  • MicroRNAs
  • Transcription Factors