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Neuroblastoma cells depend on HDAC11 for mitotic cell cycle progression and survival

Theresa M Thole1,2,3, Marco Lodrini1,3, Johannes Fabian3

  • 1Department of Pediatric Hematology, Oncology and SCT, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, Berlin 13353, Germany.

Cell Death & Disease
|March 3, 2017
PubMed

Insights

Histone deacetylase 11 (HDAC11) is crucial for neuroblastoma cell survival and proliferation. Inhibiting HDAC11 triggers cell death and may offer a new therapeutic strategy for high-risk neuroblastoma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • High-risk neuroblastoma has poor survival rates (20% at 10 years) due to treatment resistance and relapse.
  • Novel therapeutic targets are urgently needed to improve outcomes for these patients.
  • Understanding the role of specific histone deacetylases (HDACs) may lead to targeted therapies.

Purpose of the Study:

  • To investigate the function of HDAC11 in MYCN-driven neuroblastoma.
  • To identify potential therapeutic targets for high-risk neuroblastoma.

Main Methods:

  • Depletion of HDAC11 in MYCN-driven neuroblastoma cell lines.
  • Whole-genome expression analysis to identify regulated genes.
  • Functional rescue experiments with candidate genes.
  • Correlation analysis with patient survival data.

Main Results:

  • HDAC11 depletion induced significant cell death, primarily through apoptosis.
  • Genes promoting mitotic cell cycle progression (e.g., CENPA, KIF14) were repressed upon HDAC11 depletion.
  • High expression of these cell cycle genes correlated with poor patient survival.
  • RACGAP1, a cell cycle gene, partially rescued apoptosis when its expression was restored.

Conclusions:

  • HDAC11 plays a critical role in the survival and mitotic progression of MYCN-amplified neuroblastoma cells.
  • HDAC11 regulates a set of cell cycle genes that are both essential for tumor cell viability and predictive of poor patient outcomes.
  • HDAC11 represents a promising therapeutic target for high-risk neuroblastoma.

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