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

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• 作者：Sidong Huang ; Jamila Laoukili ; Mirjam T. Epping ; Jan Koster ; Michael Hö ; lzel ; Bart A. Westerman ; Wouter Nijkamp ; Akiko Hata ; Shahab Asgharzadeh ; Robert C. Seeger ; Rogier Versteeg ; Roderick L. Beijersbergen ; René ; Bernards
• 刊名：Cancer Cell
• 出版年：2009
• 出版时间：7 April 2009
• 年：2009
• 卷：15
• 期：4
• 页码：328-340
• 全文大小：1768 K

文摘

Summary

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.