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The PRC2 molecule EED is a target of epigenetic therapy for neuroblastoma

Dilibaerguli Shaliman1, Hisanori Takenobu2, Ryuichi P Sugino2

  • 1Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama, Japan; Laboratory of Tumor Molecular Biology, Department of Graduate School of Science and Engineering, Saitama University, Saitama, Japan.

European Journal of Cell Biology
|May 31, 2022
PubMed

Insights

Embryonic ectoderm development (EED) inhibition suppresses neuroblastoma (NB) growth by reactivating cell cycle and differentiation genes. Combined EED and HDAC inhibition offers a promising epigenetic therapy for aggressive NB.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Polycomb repressive complex (PRC) molecules are implicated in neuroblastoma (NB) tumorigenesis.
  • Embryonic ectoderm development (EED), a PRC2 component, interacts with H3K27me3 marks, influencing gene expression.

Purpose of the Study:

  • To investigate the molecular role of EED in MYCN-amplified NB cells.
  • To evaluate the therapeutic potential of targeting EED in NB.

Main Methods:

  • Utilized EED-knockdown (KD) shRNAs, EED-knockout sgRNAs, and the EED inhibitor EED226.
  • Performed transcriptome analysis (microarrays) and Gene Set Enrichment Analysis (GSEA).
  • Conducted ChIP sequencing and epigenetic treatments with EED226 and HDAC inhibitors (valproic acid/SAHA).

Main Results:

  • EED suppression significantly inhibited NB cell proliferation and colony formation.
  • Transcriptome analysis revealed de-repression of cell cycle and differentiation genes upon EED KD.
  • Combined EED and HDAC inhibition synergistically suppressed NB growth and upregulated key genes.

Conclusions:

  • EED plays a critical role in NB cell proliferation and aggressiveness.
  • Targeting EED, especially in combination with HDAC inhibitors, presents a viable epigenetic therapeutic strategy for NB.
  • Epigenetic reprogramming underlies the observed gene de-repression in MYCN-amplified NB.
Keywords:
EEDHistone codeNeuroblastomaPolycomb

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