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Nonsense-mediated RNA decay and its bipolar function in cancer
Molecular Cancer ( IF 37.3 ) Pub Date : 2021-04-29 , DOI: 10.1186/s12943-021-01364-0
Gonçalo Nogueira 1, 2 , Rafael Fernandes 1, 2 , Juan F García-Moreno 1, 2 , Luísa Romão 1, 2
Affiliation  

Nonsense-mediated decay (NMD) was first described as a quality-control mechanism that targets and rapidly degrades aberrant mRNAs carrying premature termination codons (PTCs). However, it was found that NMD also degrades a significant number of normal transcripts, thus arising as a mechanism of gene expression regulation. Based on these important functions, NMD regulates several biological processes and is involved in the pathophysiology of a plethora of human genetic diseases, including cancer. The present review aims to discuss the paradoxical, pro- and anti-tumorigenic roles of NMD, and how cancer cells have exploited both functions to potentiate the disease. Considering recent genetic and bioinformatic studies, we also provide a comprehensive overview of the present knowledge of the advantages and disadvantages of different NMD modulation-based approaches in cancer therapy, reflecting on the challenges imposed by the complexity of this disease. Furthermore, we discuss significant advances in the recent years providing new perspectives on the implications of aberrant NMD-escaping frameshifted transcripts in personalized immunotherapy design and predictive biomarker optimization. A better understanding of how NMD differentially impacts tumor cells according to their own genetic identity will certainly allow for the application of novel and more effective personalized treatments in the near future.

中文翻译:

无义介导的 RNA 衰变及其在癌症中的双极功能

无义介导的衰变 (NMD) 最初被描述为一种质量控制机制,它靶向并快速降解携带过早终止密码子 (PTC) 的异常 mRNA。然而,发现 NMD 也会降解大量的正常转录物,从而作为基因表达调控的一种机制出现。基于这些重要功能,NMD 调节多种生物过程,并参与包括癌症在内的多种人类遗传疾病的病理生理学。本综述旨在讨论 NMD 矛盾的、促肿瘤发生和抗肿瘤发生的作用,以及癌细胞如何利用这两种功能来加强这种疾病。考虑到最近的遗传和生物信息学研究,我们还全面概述了目前关于癌症治疗中不同基于 NMD 调制的方法的优缺点的知识,反映了这种疾病的复杂性带来的挑战。此外,我们讨论了近年来的重大进展,为异常 NMD 转码转录本在个性化免疫治疗设计和预测性生物标志物优化中的影响提供了新的视角。更好地了解 NMD 如何根据其自身的遗传特性对肿瘤细胞产生不同的影响,肯定会在不久的将来应用新的和更有效的个性化治疗。我们讨论了近年来的重大进展,就异常 NMD 转码转录本在个性化免疫治疗设计和预测性生物标志物优化中的影响提供了新的视角。更好地了解 NMD 如何根据其自身的遗传特性对肿瘤细胞产生不同的影响,肯定会在不久的将来应用新的和更有效的个性化治疗。我们讨论了近年来的重大进展,就异常 NMD 转码转录本在个性化免疫治疗设计和预测性生物标志物优化中的影响提供了新的视角。更好地了解 NMD 如何根据其自身的遗传特性对肿瘤细胞产生不同的影响,肯定会在不久的将来应用新的和更有效的个性化治疗。
更新日期:2021-04-29
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