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

doi:https://doi.org/10.1016/j.ccr.2009.02.023

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

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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 language	English
Pages (from-to)	328-340
Number of pages	13
Journal	Cancer cell
Volume	15
Issue number	4
DOIs	https://doi.org/10.1016/j.ccr.2009.02.023
Publication status	Published - 7 Apr 2009

Keywords

CELLCYCLE

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Huang, S., Laoukili, J., Epping, M. T., Koster, J., Hölzel, M., Westerman, B. A., Nijkamp, W., Hata, A., Asgharzadeh, S., Seeger, R. C., Versteeg, R., Beijersbergen, R. L., & Bernards, R. (2009). ZNF423 Is Critically Required for Retinoic Acid-Induced Differentiation and Is a Marker of Neuroblastoma Outcome. Cancer cell, 15(4), 328-340. https://doi.org/10.1016/j.ccr.2009.02.023

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

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.",

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author = "Sidong Huang and Jamila Laoukili and Epping, {Mirjam T.} and Jan Koster and Michael H{\"o}lzel and Westerman, {Bart A.} and Wouter Nijkamp and Akiko Hata and Shahab Asgharzadeh and Seeger, {Robert C.} and Rogier Versteeg and Beijersbergen, {Roderick L.} and Ren{\'e} Bernards",

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Huang, S, Laoukili, J, Epping, MT, Koster, J, Hölzel, M, Westerman, BA, Nijkamp, W, Hata, A, Asgharzadeh, S, Seeger, RC, Versteeg, R, Beijersbergen, RL & Bernards, R 2009, 'ZNF423 Is Critically Required for Retinoic Acid-Induced Differentiation and Is a Marker of Neuroblastoma Outcome', Cancer cell, vol. 15, no. 4, pp. 328-340. https://doi.org/10.1016/j.ccr.2009.02.023

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AU - Huang, Sidong

AU - Laoukili, Jamila

AU - Epping, Mirjam T.

AU - Koster, Jan

AU - Hölzel, Michael

AU - Westerman, Bart A.

AU - Nijkamp, Wouter

AU - Hata, Akiko

AU - Asgharzadeh, Shahab

AU - Seeger, Robert C.

AU - Versteeg, Rogier

AU - Beijersbergen, Roderick L.

AU - Bernards, René

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AB - 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.

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JO - Cancer cell

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

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Keywords

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