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Updated: Oct 23, 2025

Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy
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TOP2B Enzymatic Activity on Promoters and Introns Modulates Multiple Oncogenes in Human Gliomas

Edgar Gonzalez-Buendia1, Junfei Zhao2, Lu Wang3

  • 1Department of Neurosurgery, Feinberg School of Medicine, Northwestern University and Northwestern Medicine Malnati Brain Tumor Institute of the Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|August 26, 2021
PubMed
Abstract

Insights

Topoisomerase IIB (TOP2B) promotes glioma proliferation by epigenetically regulating oncogenes like PDGFRA and MYC. Inhibiting TOP2B in gliomas enhances survival and downregulates PDGFRA, offering a potential therapeutic target.

Area of Science:

  • Epigenetics and transcriptional regulation in oncology.
  • Mechanisms of malignant transformation in brain tumors.

Background:

  • Epigenetic mechanisms driving glioma malignancy are not fully understood.
  • Topoisomerase IIB (TOP2B), involved in DNA dynamics, is overexpressed in some gliomas.

Purpose of the Study:

  • To investigate the role of TOP2B in epigenetic regulation within gliomas.
  • To determine TOP2B's contribution to the malignant phenotype of gliomas.

Main Methods:

  • Paired chromatin immunoprecipitation sequencing (ChIP-seq) for TOP2B and RNA-sequencing.
  • Assay for transposase-accessible chromatin using sequencing (ATAC-seq).
  • Gene silencing and mouse xenograft models were utilized.

Main Results:

  • TOP2B actively modulates transcription of multiple oncogenes, including PDGFRA and MYC, at specific genomic locations (enhancers, promoters, introns).
  • TOP2B expression and localization correlate with PDGFRA and MYC levels in gliomas but not normal brain tissue.
  • TOP2B inhibition in vivo prolonged survival and reduced PDGFRA expression in glioma models.

Conclusions:

  • TOP2B plays a significant role in the transcriptional regulation of oncogenes in a subset of gliomas.
  • TOP2B activity promotes a proliferative phenotype in gliomas through epigenetic mechanisms.
  • Targeting TOP2B may offer a therapeutic strategy for specific glioma subtypes.

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