Up-regulated microRNA-299 corrected with poor prognosis of glioblastoma multiforme patients by targeting ELL2

Jpn J Clin Oncol. 2017 Jul 1;47(7):590-596. doi: 10.1093/jjco/hyw188.

Abstract

Background: An increasing understanding of the genes and molecular pathways of glioblastoma multiforme (GBM) can provide us a useful insight for the development of more effective targeted therapeutic.

Methods: To investigate the expression and clinical significance of miR-299 and its target genes in GBM, the expression levels of miR-299 and its target gene in human normal brain tissues and GBM were analyzed in silico using genes microarray and hierarchical clustering analysis followed by validation with quantitative RT-PCR.

Results: Our results show that miR-299 is up-regulated in GBM patients. Moreover, patients with low miR-299 expression had longer overall survival (OS) compared with those with high miR-299 expression. RNA polymerase II elongation factor, ELL2, was identified as a miR-299 direct target. High expression of ELL2 together with miR-299 down-regulation correlated with a shorter median OS.

Conclusions: Our results provide the first evidence that ELL2 is a direct target of miR-299 and increased ELL2 expression and down-regulation of miR-299 are associated with GBM progression and poor prognosis in patients, suggesting that ELL2 and miR-299 might have potential prognostic value and be used as tumor biomarkers for the diagnosis of patients with GBM.

Keywords: ELL2; GBM; microRNA-299; prognosis.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Glioblastoma / genetics*
  • Glioblastoma / metabolism
  • Glioblastoma / pathology
  • Humans
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Microarray Analysis
  • Prognosis
  • Transcriptional Elongation Factors / genetics*
  • Transcriptional Elongation Factors / metabolism
  • Transfection
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • ELL2 protein, human
  • MIRN299 microRNA, human
  • MicroRNAs
  • Transcriptional Elongation Factors