锌指蛋白423（ZNF423）是维甲酸诱导分化所必需的关键因子，也是神经母细胞瘤预后的一个标志物。
ZNF423 is critically required for retinoic acid-induced differentiation and is a marker of neuroblastoma outcome.
作者信息
Huang Sidong, Laoukili Jamila, Epping Mirjam T, Koster Jan, Hölzel Michael, Westerman Bart A, Nijkamp Wouter, Hata Akiko, Asgharzadeh Shahab, Seeger Robert C, Versteeg Rogier, Beijersbergen Roderick L, Bernards René
机构信息
Division of Molecular Carcinogenesis, Center for Biomedical Genetics and Cancer Genomics Center, The Netherlands Cancer Institute (NKI), Amsterdam, The Netherlands.
出版信息
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.
维甲酸在细胞分化、生长停滞和细胞凋亡中发挥关键作用，并且越来越多地在临床上用于治疗包括神经母细胞瘤在内的多种癌症。在此，我们通过基于RNA干扰的大规模基因筛选，鉴定出ZNF423（也称为Ebfaz、OAZ或Zfp423）是维甲酸（RA）诱导分化所必需的关键成分。ZNF423与RARα/RXRα核受体复合物相关联，并且对于维甲酸响应的反式激活至关重要。在神经母细胞瘤细胞中通过RNA干扰下调ZNF423表达会导致生长优势和对RA诱导分化的抗性，而ZNF423的过表达则导致生长抑制和增强的分化。最后，我们表明低ZNF423表达与神经母细胞瘤患者的不良疾病预后相关。
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