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 in | Molecular cancer Vol. 20; no. 1; p. 72 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
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BioMed Central
29.04.2021
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Abstract | 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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AbstractList | Abstract 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. 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. |
ArticleNumber | 72 |
Author | Nogueira, Gonçalo Romão, Luísa García-Moreno, Juan F Fernandes, Rafael |
Author_xml | – sequence: 1 givenname: Gonçalo surname: Nogueira fullname: Nogueira, Gonçalo organization: BioISI - Instituto de Biossistemas e Ciências Integrativas, Faculdade de Ciências, Universidade de Lisboa, 1749-016, Lisbon, Portugal – sequence: 2 givenname: Rafael surname: Fernandes fullname: Fernandes, Rafael organization: BioISI - Instituto de Biossistemas e Ciências Integrativas, Faculdade de Ciências, Universidade de Lisboa, 1749-016, Lisbon, Portugal – sequence: 3 givenname: Juan F surname: García-Moreno fullname: García-Moreno, Juan F organization: BioISI - Instituto de Biossistemas e Ciências Integrativas, Faculdade de Ciências, Universidade de Lisboa, 1749-016, Lisbon, Portugal – sequence: 4 givenname: Luísa orcidid: 0000-0002-5061-5287 surname: Romão fullname: Romão, Luísa email: luisa.romao@insa.min-saude.pt, luisa.romao@insa.min-saude.pt organization: BioISI - Instituto de Biossistemas e Ciências Integrativas, Faculdade de Ciências, Universidade de Lisboa, 1749-016, Lisbon, Portugal. luisa.romao@insa.min-saude.pt |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/33926465$$D View this record in MEDLINE/PubMed |
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Keywords | Biomarker Tumor microenvironment Cancer therapy Immunotherapy Oncogene Nonsense-mediated RNA decay (NMD) Neoantigen Environmental stress Tumor suppressor gene |
Language | English |
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Snippet | Nonsense-mediated decay (NMD) was first described as a quality-control mechanism that targets and rapidly degrades aberrant mRNAs carrying premature... Abstract Nonsense-mediated decay (NMD) was first described as a quality-control mechanism that targets and rapidly degrades aberrant mRNAs carrying premature... |
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StartPage | 72 |
SubjectTerms | 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 |
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Title | Nonsense-mediated RNA decay and its bipolar function in cancer |
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