ZNF423 Is Critically Required for Retinoic Acid-Induced Differentiation and Is a Marker of Neuroblastoma Outcome

Sidong Huang, Jamila Laoukili, Mirjam T. Epping, Jan Koster, Michael Hölzel, Bart A. Westerman, Wouter Nijkamp, Akiko Hata, Shahab Asgharzadeh, Robert C. Seeger, Rogier Versteeg, Roderick L. Beijersbergen, René Bernards*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Retinoids play key roles in differentiation, growth arrest, and apoptosis and are increasingly being used in the clinic for the treatment of a variety of cancers, including neuroblastoma. Here, using a large-scale RNA interference-based genetic screen, we identify ZNF423 (also known as Ebfaz, OAZ, or Zfp423) as a component critically required for retinoic acid (RA)-induced differentiation. ZNF423 associates with the RARα/RXRα nuclear receptor complex and is essential for transactivation in response to retinoids. Downregulation of ZNF423 expression by RNA interference in neuroblastoma cells results in a growth advantage and resistance to RA-induced differentiation, whereas overexpression of ZNF423 leads to growth inhibition and enhanced differentiation. Finally, we show that low ZNF423 expression is associated with poor disease outcome in neuroblastoma patients.

Original languageEnglish
Pages (from-to)328-340
Number of pages13
JournalCancer Cell
Volume15
Issue number4
DOIs
Publication statusPublished - 7 Apr 2009

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