Nonsense-mediated RNA decay and its bipolar function in cancer

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...

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Published inMolecular cancer Vol. 20; no. 1; p. 72
Main Authors Nogueira, Gonçalo, Fernandes, Rafael, García-Moreno, Juan F, Romão, Luísa
Format Journal Article
LanguageEnglish
Published England BioMed Central 29.04.2021
BMC
Subjects
Biomarker
Cancer
Cancer therapy
Cell cycle
Codons
Gene expression
Gene regulation
Immunotherapy
Kinases
Mutation
Neoantigen
Nonsense-mediated RNA decay (NMD)
Peptides
Phosphorylation
Proteins
Quality control
Review
Tumor cells
Tumor suppressor gene
Tumorigenesis
Biomarker
Tumor microenvironment
Cancer therapy
Immunotherapy
Oncogene
Nonsense-mediated RNA decay (NMD)
Neoantigen
Environmental stress
Tumor suppressor gene
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Summary: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.
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ISSN:1476-4598
1476-4598
DOI:10.1186/s12943-021-01364-0