Inhibition of EGR1 inhibits glioma proliferation by targeting CCND1 promoter

J Exp Clin Cancer Res. 2017 Dec 15;36(1):186. doi: 10.1186/s13046-017-0656-4.

Abstract

Background: Gliomas are the most common primary tumors in central nervous system. The prognosis of the patients with glioma is poor regardless of the development of therapeutic strategies. Its aggressive behavior mainly depends on the potent ability of proliferation. The transcription factor EGR1 (early growth response 1) is a member of a zinc finger transcription factor family which plays an essential role in cell growth and proliferation.

Methods: EGR1 expression levels in 39 glioma tissues and 10 normal brain tissues were tested by RT-qPCR and Western-blotting. The effects of EGR1 on U251 cells, U251 stem-like cells (GSCs), and U87 cells proliferation were assessed using in vitro and in vivo cell proliferation assays. The specific binding between EGR1 and CCND1 promoter was confirmed by CHIP assay. EGF was used to improve EGR1 expression in this assay.

Results: EGR1 expression levels in human gliomas are decreased compared with normal brain tissues, however, the patients with low EGR1 expression level showed significantly enhanced patient survival in all glioma patients. EGR1 silencing inhibited proliferation and induced G1 phase arrest in glioma cells. EGR1 contributed to proliferation by directly raising CCND1. Meanwhile, EGR1 overexpression induced by EGF was able to promote the proliferation of glioma cells.

Conclusions: Our results show that stable knockdown EGR1 would inhibit glioma proliferation. The results suggest EGR1 showing lower expression in cancer tissues compared with normal tissues maybe still play an important role in tumor proliferation.

Keywords: CCND1; EGR1; Glioma; Proliferation.

MeSH terms

  • Animals
  • Brain Neoplasms / pathology*
  • Cell Proliferation / physiology
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism*
  • Early Growth Response Protein 1 / metabolism*
  • Gene Expression Regulation, Neoplastic / physiology*
  • Glioma / pathology*
  • Humans
  • Mice
  • Mice, SCID
  • Promoter Regions, Genetic / genetics

Substances

  • CCND1 protein, human
  • EGR1 protein, human
  • Early Growth Response Protein 1
  • Cyclin D1