ZNF423 is critically required for retinoic acid-induced differentiation and is a marker of neuroblastoma outcome

Cancer Cell. 2009 Apr 7;15(4):328-40. doi: 10.1016/j.ccr.2009.02.023.


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 RARalpha/RXRalpha 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antineoplastic Agents / pharmacology*
  • Cell Differentiation*
  • Child
  • Child, Preschool
  • Chromatin Immunoprecipitation
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Neuroblastoma / metabolism*
  • Neuroblastoma / pathology*
  • Prognosis
  • Promoter Regions, Genetic
  • Proteins
  • Receptors, Retinoic Acid / genetics
  • Receptors, Retinoic Acid / metabolism
  • Retinoic Acid Receptor alpha
  • Survival Rate
  • Teratocarcinoma / metabolism
  • Teratocarcinoma / pathology
  • Tretinoin / pharmacology*
  • Zinc Fingers


  • Antineoplastic Agents
  • DNA-Binding Proteins
  • Proteins
  • RARA protein, human
  • Receptors, Retinoic Acid
  • Retinoic Acid Receptor alpha
  • ornithine decarboxylase antizyme
  • Tretinoin

Associated data

  • GEO/GSE14627