Molecular Mechanisms of MYCN Dysregulation in Cancers.

Molecular Mechanisms of MYCN Dysregulation in Cancers.
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DOI:
10.3389/fonc.2020.625332
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发表时间:
2020
影响因子:
4.7
通讯作者:
Cui H
Cui H
中科院分区:
医学3区
文献类型:
--
作者:
Liu R;Shi P;Wang Z;Yuan C;Cui H

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MYCN是MYC原癌基因家族的成员,编码一种碱性螺旋-环-螺旋转录因子N-MYC。N-MYC的异常表达与肿瘤的高危和预后不良有关。1983年,N-MYC最初被确定为神经母细胞瘤中的一种扩增癌基因,其致癌作用已扩展到多发性神经性和非神经性肿瘤。直接瞄准N-MYC仍然是一个挑战,因为它具有“不可下药”的特点。因此,针对MYCN驱动的肿瘤的替代治疗方法一直集中在MYCN的转录、翻译、蛋白质稳定性以及合成杀伤力的破坏上。在这篇综述中,我们总结了在理解MYCN在癌症中的分子机制方面的最新进展。
MYCN, a member of MYC proto-oncogene family, encodes a basic helix-loop-helix transcription factor N-MYC. Abnormal expression of N-MYC is correlated with high-risk cancers and poor prognosis. Initially identified as an amplified oncogene in neuroblastoma in 1983, the oncogenic effect of N-MYC is expanded to multiple neuronal and nonneuronal tumors. Direct targeting N-MYC remains challenge due to its “undruggable” features. Therefore, alternative therapeutic approaches for targeting MYCN-driven tumors have been focused on the disruption of transcription, translation, protein stability as well as synthetic lethality of MYCN. In this review, we summarize the latest advances in understanding the molecular mechanisms of MYCN dysregulation in cancers.
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