MiR-215, an activator of the CTNNBIP1/β-catenin pathway, is a marker of poor prognosis in human glioma

Oncotarget. 2015 Sep 22;6(28):25024-33. doi: 10.18632/oncotarget.4622.

Abstract

MicroRNA-215 (miR-215) promotes tumor growth in various human malignancies. However, its role has not yet been determined in human glioma. Here, we found that levels of miR-215 were higher in glioma tissues than in corresponding non-neoplastic brain tissue. High miR-215 expression was correlated with higher World Health Organization (WHO) grades and shorter overall survival. Multivariate and univariate analysis indicated that miR-215 expression was an independent prognostic factor. We also found that TGF-beta1, phosphorylated beta-catenin, alpha-SMA, and fibronectin were increased in glioma tissues. Additionally, CTNNBIP1, a direct target of miR-215, was decreased in glioma compared to adjacent normal tissue. These data indicate that miR-215 activates Wnt/β-catenin signaling by increasing β-catenin phosphorylation, α-SMA expression, and fibronectin expression. It promotes TGF-β1-induced oncogenesis by suppressing CTNNBIP1 in glioma. In summary, miR-215 is overexpressed in human glioma, is involved in TGF-β1-induced oncogenesis, and can be used as a marker of poor prognosis in glioma patients.

Keywords: CTNNBIP1; TGF-β1; glioma; miR-215; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adult
  • Aged
  • Biomarkers, Tumor / genetics*
  • Blotting, Western / statistics & numerical data
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Female
  • Fibronectins / metabolism
  • Gene Expression Regulation, Neoplastic
  • Glioma / genetics*
  • Glioma / metabolism
  • Glioma / pathology
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Kaplan-Meier Estimate
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Multivariate Analysis
  • Prognosis
  • Proportional Hazards Models
  • Reverse Transcriptase Polymerase Chain Reaction / statistics & numerical data
  • Transforming Growth Factor beta1 / metabolism
  • Wnt Signaling Pathway / genetics
  • Young Adult
  • beta Catenin / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor
  • CTNNBIP1 protein, human
  • Fibronectins
  • Intracellular Signaling Peptides and Proteins
  • MIRN215 microRNA, human
  • MicroRNAs
  • Transforming Growth Factor beta1
  • beta Catenin