裸鼹鼠作为一种具有高度抗癌能力的模型中的翻译调控。

Translational control in the naked mole-rat as a model highly resistant to cancer.

机构信息

From the Translation and Cancer Laboratory, Unit of Biomedical Research on Cancer, National Institute of Cancer (Instituto Nacional de Cancerología, INCan), 22 San Fernando Ave., Tlalpan, 14080 Mexico City, Mexico.

出版信息

Biochim Biophys Acta Rev Cancer. 2021 Jan;1875(1):188455. doi: 10.1016/j.bbcan.2020.188455. Epub 2020 Oct 22.

DOI:10.1016/j.bbcan.2020.188455

PMID:33148499

Abstract

Dysregulation of mRNA translation is involved in the onset and progression of different types of cancer. To gain insight into novel genetic strategies to avoid this malady, we reviewed the available genomic, transcriptomic, and proteomic data about the translational machinery from the naked-mole rat (NMR) Heterocephalus glaber, a new model of study that exhibits high resistance to cancer. The principal features that might confer cancer resistance are 28S rRNA fragmentation, RPL26 and eIF4G overexpression, global downregulation of mTOR pathway, specific amino acid residues in RAPTOR (P908) and RICTOR (V1695), and the absence of 4E-BP3. These features are not only associated with cancer but also might couple longevity and adaptation to hypoxia. We propose that the regulation of translation is among the strategies endowing NMR cancer resistance.

摘要

mRNA 翻译的失调与不同类型癌症的发生和发展有关。为了深入了解避免这种疾病的新的遗传策略，我们回顾了裸鼹鼠（NMR） Heterocephalus glaber 中翻译机制的可用基因组、转录组和蛋白质组数据，裸鼹鼠是一种具有高抗癌能力的新型研究模型。赋予癌症抗性的主要特征是 28S rRNA 片段化、RPL26 和 eIF4G 过表达、mTOR 通路的全局下调、RAPTOR（P908）和 RICTOR（V1695）中的特定氨基酸残基以及 4E-BP3 的缺失。这些特征不仅与癌症有关，还可能与长寿和适应低氧有关。我们提出，翻译的调控是赋予 NMR 抗癌能力的策略之一。