Overexpressed KDM5B is associated with the progression of glioma and promotes glioma cell growth via downregulating p21

Biochem Biophys Res Commun. 2014 Nov 7;454(1):221-7. doi: 10.1016/j.bbrc.2014.10.078. Epub 2014 Oct 22.

Abstract

Epigenetic alterations such as aberrant expression of histone-modifying enzymes have been implicated in tumorigenesis. Upregulation of lysine (K)-specific demethylase 5B (KDM5B) has been reported in a variety of malignant tumors. However, the impact of KDM5B in glioma remains unclear. The objective of this study was to investigate the expression and prognostic value of KDM5B in glioma. In clinical glioma samples, we found that KDM5B expression was significantly upregulated in cancer lesions compared with normal brain tissues. Kaplan-Meier analysis showed that patients with glioma and higher KDM5B expression tend to have shorter overall survival time. By silencing or overexpressing KDM5B in glioma cells, we found that KDM5B could promote cell growth both in vitro and in vivo. Moreover, we demonstrated that KDM5B promoted glioma proliferation partly via regulation of the expression of p21. Our study provided evidence that KDM5B functions as a novel tumor oncogene in glioma and may be a potential therapeutic target for glioma management.

Keywords: Glioma; KDM5B; Proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Brain / metabolism
  • Brain / pathology
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Case-Control Studies
  • Cell Line, Tumor
  • Cell Proliferation
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics*
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism*
  • Disease Progression
  • Down-Regulation
  • Epigenesis, Genetic
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Glioma / genetics*
  • Glioma / metabolism*
  • Glioma / pathology
  • Heterografts
  • Humans
  • Jumonji Domain-Containing Histone Demethylases / antagonists & inhibitors
  • Jumonji Domain-Containing Histone Demethylases / genetics*
  • Jumonji Domain-Containing Histone Demethylases / metabolism*
  • Mice
  • Mice, Nude
  • Nuclear Proteins / antagonists & inhibitors
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism*
  • Oncogenes
  • Repressor Proteins / antagonists & inhibitors
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism*
  • Tumor Stem Cell Assay
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Nuclear Proteins
  • Repressor Proteins
  • Jumonji Domain-Containing Histone Demethylases
  • KDM5B protein, human