ZNF423 is Critically Required for Retinoic Acid-induced Differentiation and is a Marker of Neuroblastoma Outcome

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2009 Apr 7

PMID 19345331

Citations 87

Authors

Sidong Huang

Jamila Laoukili

Mirjam T Epping

Jan Koster

Michael Holzel

Bart A Westerman

Wouter Nijkamp

Akiko Hata

Shahab Asgharzadeh

Robert C Seeger

Rogier Versteeg

Roderick L Beijersbergen

Rene Bernards

Affiliations

Soon will be listed here.

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 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.

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