HOXA13 is a potential GBM diagnostic marker and promotes glioma invasion by activating the Wnt and TGF-β pathways

Oncotarget. 2015 Sep 29;6(29):27778-93. doi: 10.18632/oncotarget.4813.

Abstract

Homeobox (HOX) genes, including HOXA13, are involved in human cancer. We found that HOXA13 expression was associated with glioma grade and prognosis. Bioinformatics analysis revealed that most of the HOXA13-associated genes were enriched in cancer-related signaling pathways and mainly involved in the regulation of transcription. We transfected four glioma cell lines with Lenti-si HOXA13. HOXA13 increased cell proliferation and invasion and inhibited apoptosis. HOXA13 decreased β-catenin, phospho-smad2, and phospho-smad3 in the nucleus and increased phospho-β-catenin in the cytoplasm. Furthermore, downregulation of HOXA13 in orthotopic tumors decreased tumor growth. We suggest that HOXA13 promotes glioma progression in part via Wnt- and TGF-β-induced EMT and is a potential diagnostic biomarker for glioblastoma and an independent prognostic factor in high-grade glioma.

Keywords: HOXA13; Homeobox (HOX) gene; SMAD; epithelial-to-mesenchymal transition (EMT); glioma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Apoptosis
  • Biomarkers, Tumor / metabolism*
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Computational Biology
  • Cytoplasm / metabolism
  • Disease Progression
  • Epithelial-Mesenchymal Transition
  • Female
  • Glioma / metabolism*
  • Glioma / pathology
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Middle Aged
  • Neoplasm Invasiveness
  • Prognosis
  • Proportional Hazards Models
  • Smad2 Protein / metabolism
  • Smad3 Protein / metabolism
  • Transforming Growth Factor beta1 / metabolism*
  • Wnt Signaling Pathway*
  • Young Adult
  • beta Catenin / metabolism

Substances

  • Biomarkers, Tumor
  • CTNNB1 protein, human
  • Homeodomain Proteins
  • SMAD2 protein, human
  • SMAD3 protein, human
  • Smad2 Protein
  • Smad3 Protein
  • TGFB1 protein, human
  • Transforming Growth Factor beta1
  • beta Catenin
  • homeobox protein HOXA13