文章：

癌症基因组翻译控制的新领域

New frontiers in translational control of the cancer genome

原文发布日期：2016-04-26

DOI: 10.1038/nrc.2016.27

类型: Review Article

开放获取: 否

要点：

1. Oncogenic signalling rewires the translational machinery to support the expression of specific functional classes of pro-tumorigenic genes.
2. An expanding list of structural and sequence-specific cis-regulatory elements control expression of the oncogenic translation programme.
3. Specific trans-acting factors, such as RNA-binding proteins, interact with cis-regulatory elements to dictate mRNA translation in cancer cells.
4. Tumour cells alter tRNA expression and modification patterns to match the codon-usage bias of mRNA networks that support the transformed phenotype.
5. Translational control is crucial for the adaptive response to tumour-associated stress and represents a new therapeutic target for selectively killing cancer cells.
6. Recent technological advances in profiling genome-wide translation, RNA–protein interactions, RNA structure, RNA modifications and tRNA expression are driving a new understanding of the molecular mechanisms underlying translational control in cancer.

要点翻译：

1. 致癌信号重编程翻译机制，以支持特定功能类别的促肿瘤基因表达。
2. 不断增多的结构性和序列特异性顺式调控元件控制着致癌翻译程序的表达。
3. 特异性反式作用因子（如RNA结合蛋白）与顺式调控元件相互作用，决定癌细胞中mRNA的翻译。
4. 肿瘤细胞通过改变tRNA表达和修饰模式，以适应支持转化表型的mRNA网络的密码子使用偏好。
5. 翻译控制对于肿瘤相关应激的适应性响应至关重要，并为选择性杀伤癌细胞提供了新的治疗靶点。
6. 近期在全基因组翻译谱分析、RNA-蛋白质相互作用、RNA结构、RNA修饰及tRNA表达方面的技术进展，正推动对癌症翻译控制分子机制的新认知。

英文摘要：

The past several years have seen dramatic leaps in our understanding of how gene expression is rewired at the translation level during tumorigenesis to support the transformed phenotype. This work has been driven by an explosion in technological advances and is revealing previously unimagined regulatory mechanisms that dictate functional expression of the cancer genome. In this Review we discuss emerging trends and exciting new discoveries that reveal how this translational circuitry contributes to specific aspects of tumorigenesis and cancer cell function, with a particular focus on recent insights into the role of translational control in the adaptive response to oncogenic stress conditions.

摘要翻译： 

过去几年，我们在理解肿瘤发生过程中基因表达如何在翻译层面被重编程以支持转化表型方面取得了飞跃性进展。这一进展由技术爆炸所驱动，揭示出此前难以想象的调控机制，它们决定着癌症基因组的功能性表达。在本综述中，我们讨论新兴趋势和令人振奋的新发现，阐明这一翻译回路如何促进肿瘤发生及癌细胞功能的特定方面，并重点聚焦翻译控制在应对癌基因应激条件适应性反应中的最新认识。

原文链接：

New frontiers in translational control of the cancer genome