Neuroblastoma (NB) is the most common solid tumor in childhood. Twenty percent of patients display MYCN amplification, which indicates a very poor prognosis. MYCN is a highly specific target for an NB tumor therapy as MYCN expression is absent or very low in most normal cells, while, as a transcription factor, it regulates many essential cell activities in tumor cells. We aim to develop a therapy for NB based on MYCN silencing by short interfering RNA (siRNA) molecules, which can silence target genes by RNA interference (RNAi), a naturally occurring method of gene silencing. It has been shown previously that MYCN silencing can induce apoptosis and differentiation in MYCN amplified NB. In this article, we have demonstrated that siRNA-mediated silencing of MYCN in MYCN-amplified NB cells induced neurogenesis in NB cells, whereas retinoic acid (RA) treatment did not. RA can differentiate NB cells and is used for treatment of residual disease after surgery or chemotherapy, but resistance can develop. In addition, MYCN siRNA treatment suppressed growth in a MYCN-amplified NB cell line more than that by RA. Our result suggests that gene therapy using RNAi targeting MYCN can be a novel therapy toward MYCN-amplified NB that have complete or partial resistance toward RA.

中文翻译：

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在对视黄酸具有抗性的神经母细胞瘤模型中，通过 RNAi 进行的 MYCN 沉默诱导神经发生并抑制增殖。

神经母细胞瘤（NB）是儿童期最常见的实体瘤。20% 的患者显示MYCN扩增，这表明预后非常差。MYCN是 NB 肿瘤治疗的高度特异性靶标，因为在大多数正常细胞中MYCN表达不存在或非常低，而作为转录因子，它调节肿瘤细胞中的许多基本细胞活动。我们的目标是开发一种基于通过短干扰 RNA (siRNA) 分子进行MYCN沉默的NB 疗法，该疗法可以通过 RNA 干扰 (RNAi)（一种自然发生的基因沉默方法）使靶基因沉默。先前已经表明，MYCN沉默可以诱导细胞凋亡和分化MYCN放大的NB。在本文中，我们证明了MYCN扩增的 NB 细胞中 siRNA 介导的MYCN沉默诱导了 NB 细胞的神经发生，而视黄酸 (RA) 治疗则没有。RA 可以分化 NB 细胞，用于治疗手术或化疗后的残留病灶，但会产生耐药性。此外，MYCN siRNA 处理抑制MYCN扩增的 NB 细胞系中的生长比 RA抑制的更多。我们的结果表明，使用靶向MYCN 的RNAi 的基因治疗可能是一种针对MYCN扩增的 NB的新疗法，该 NB 对 RA 具有完全或部分抗性。