MYCN silencing induces differentiation and apoptosis in human neuroblastoma cells
MYCN silencing induces differentiation and apoptosis in human neuroblastoma cells
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DOI：
10.1016/j.bbrc.2006.10.020
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发表时间：
2006-12-08
影响因子：
3.1
通讯作者：
Chung, Dal H.
中科院分区：
文献类型：
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作者：
Kang, Jung-Hee;Rychahou, Piotr G.;Chung, Dal H.
神经母细胞瘤患者的MYCN扩增与不良预后密切相关。本研究的目的是探讨MYCN在神经母细胞瘤细胞分化和凋亡中的作用。我们利用RNA干扰技术抑制了MYCN可变表达神经母细胞瘤细胞中MYCN基因的表达。我们的结果表明，抑制MYCN扩增细胞中MYCN基因的表达诱导了细胞的凋亡，抑制了细胞的生长；MYCN基因沉默后也发生了神经元分化。此外，N-myc表达下调与Bclxl蛋白水平和caspase-3活性降低有关。这些数据表明，针对MYCN的小干扰RNA对神经母细胞瘤细胞的存活起着至关重要的作用，可能为侵袭性神经母细胞瘤提供潜在的新的治疗选择。(C)2006 Elsevier Inc.保留所有权利。
MYCN amplification strongly correlates with unfavorable outcomes in patients with neuroblastoma. The aim of this study was to investigate the role of MYCN in neuroblastoma cell differentiation and apoptosis. We used the technique of RNA interference to inhibit MYCN gene expression in neuroblastoma cells with variable expression of MYCN. Our results showed that inhibition of MYCN gene expression in MYCN amplified cells induced apoptosis and suppressed cell growth; neuronal differentiation also occurred after MYCN gene silencing. Moreover, N-myc downregulation was associated with decreased Bcl-xL protein levels and caspase-3 activation. These data show that small interfering RNA directed to MYCN, which plays a crucial role in neuroblastoma cell survival, may provide a potential novel therapeutic option for aggressive neuroblastomas. (c) 2006 Elsevier Inc. All rights reserved.