Repression of the expression of TET2 by ZEB1 contributes to invasion and growth in glioma cells

Mol Med Rep. 2017 May;15(5):2625-2632. doi: 10.3892/mmr.2017.6288. Epub 2017 Mar 3.

Abstract

Malignant gliomas are the most common and aggressive type of brain tumor. The suppressive role of ten-eleven translocation 2 (TET2) has been implicated in certain types of cancer, however, its role in gliomas remains to be elucidated. The present study aimed to determine the expression pattern and biological role of TET2 in glioma, using RT-qPCR and immunohistochemistry, and its results indicated that the expression of TET2 was frequently decreased in gliomas and that repression of the expression of TET2 correlated with the progression of glioma. The ectopic expression of TET2 inhibited the invasive potential of glioma cells, and inhibited glioma cell proliferation in vitro and growth in vivo. Additionally, the expression of Zinc finger E‑box‑binding homeobox 1 (ZEB1) was increased in gliomas and was positively correlated with progression, but inversely correlated with the expression of TET2. ZEB1 was also confirmed to physically bind to the TET2 promoter. ZEB1 knockdown resulted in an increase in the expression of TET2 and elevation of TET2 promoter activity in glioma cells. These findings indicated that the downregulation of TET2 by ZEB1 is a critical oncogenic event in gliomas.

MeSH terms

  • Aged
  • Animals
  • Brain / metabolism
  • Brain / pathology
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Chromatin Immunoprecipitation
  • DNA-Binding Proteins / antagonists & inhibitors
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Dioxygenases
  • Female
  • Glioma / metabolism
  • Glioma / mortality
  • Glioma / pathology*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Promoter Regions, Genetic
  • Protein Binding
  • Proto-Oncogene Proteins / antagonists & inhibitors
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Transplantation, Heterologous
  • Zinc Finger E-box-Binding Homeobox 1 / antagonists & inhibitors
  • Zinc Finger E-box-Binding Homeobox 1 / genetics
  • Zinc Finger E-box-Binding Homeobox 1 / metabolism*

Substances

  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • RNA, Small Interfering
  • Zinc Finger E-box-Binding Homeobox 1
  • Dioxygenases
  • TET2 protein, human