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Dissecting the Functional Mechanisms of Somatic Copy-Number Alterations Based on Dysregulated ceRNA Networks across Cancers
Somatic copy-number alterations (SCNAs) drive tumor growth and evolution. However, the functional roles of SCNAs across the genome are still poorly understood. We provide an integrative strategy to characterize the functional roles of driver SCNAs in cancers based on dysregulated competing endogenou...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Gene & Cell Therapy
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358224/ https://www.ncbi.nlm.nih.gov/pubmed/32668393 http://dx.doi.org/10.1016/j.omtn.2020.06.012 |
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author | Ping, Yanyan Zhou, Yao Hu, Jing Pang, Lin Xu, Chaohan Xiao, Yun |
author_facet | Ping, Yanyan Zhou, Yao Hu, Jing Pang, Lin Xu, Chaohan Xiao, Yun |
author_sort | Ping, Yanyan |
collection | PubMed |
description | Somatic copy-number alterations (SCNAs) drive tumor growth and evolution. However, the functional roles of SCNAs across the genome are still poorly understood. We provide an integrative strategy to characterize the functional roles of driver SCNAs in cancers based on dysregulated competing endogenous RNA (ceRNA) networks. We identified 44 driver SCNAs in lower-grade glioma (LGG). The dysregulated patterns losing all correlation relationships dominated dysregulated ceRNA networks. Homozygous deletion of six genes in 9p21.3 characterized an LGG subtype with poor prognosis and contributed to the dysfunction of cancer-associated pathways in a complementary way. The pan-cancer analysis showed that different cancer types harbored different driver SCNAs through dysregulating the crosstalk with common ceRNAs. The same SCNAs destroyed their ceRNA networks through different miRNA-mediated ceRNA regulations in different cancers. Additionally, some SCNAs performed different functional mechanisms in different cancers, which added another layer of complexity to cancer heterogeneity. Compared with previous methods, our strategy could directly dissect functional roles of SCNAs from the view of ceRNA networks, which not only complemented the functions of protein-coding genes but also provided a new avenue to characterize the functions of noncoding RNAs. Also, our strategy could be applied to more types of cancers to identify pathogenic mechanism driven by the SCNAs. |
format | Online Article Text |
id | pubmed-7358224 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
spelling | pubmed-73582242020-07-20 Dissecting the Functional Mechanisms of Somatic Copy-Number Alterations Based on Dysregulated ceRNA Networks across Cancers Ping, Yanyan Zhou, Yao Hu, Jing Pang, Lin Xu, Chaohan Xiao, Yun Mol Ther Nucleic Acids Article Somatic copy-number alterations (SCNAs) drive tumor growth and evolution. However, the functional roles of SCNAs across the genome are still poorly understood. We provide an integrative strategy to characterize the functional roles of driver SCNAs in cancers based on dysregulated competing endogenous RNA (ceRNA) networks. We identified 44 driver SCNAs in lower-grade glioma (LGG). The dysregulated patterns losing all correlation relationships dominated dysregulated ceRNA networks. Homozygous deletion of six genes in 9p21.3 characterized an LGG subtype with poor prognosis and contributed to the dysfunction of cancer-associated pathways in a complementary way. The pan-cancer analysis showed that different cancer types harbored different driver SCNAs through dysregulating the crosstalk with common ceRNAs. The same SCNAs destroyed their ceRNA networks through different miRNA-mediated ceRNA regulations in different cancers. Additionally, some SCNAs performed different functional mechanisms in different cancers, which added another layer of complexity to cancer heterogeneity. Compared with previous methods, our strategy could directly dissect functional roles of SCNAs from the view of ceRNA networks, which not only complemented the functions of protein-coding genes but also provided a new avenue to characterize the functions of noncoding RNAs. Also, our strategy could be applied to more types of cancers to identify pathogenic mechanism driven by the SCNAs. American Society of Gene & Cell Therapy 2020-06-18 /pmc/articles/PMC7358224/ /pubmed/32668393 http://dx.doi.org/10.1016/j.omtn.2020.06.012 Text en © 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Ping, Yanyan Zhou, Yao Hu, Jing Pang, Lin Xu, Chaohan Xiao, Yun Dissecting the Functional Mechanisms of Somatic Copy-Number Alterations Based on Dysregulated ceRNA Networks across Cancers |
title | Dissecting the Functional Mechanisms of Somatic Copy-Number Alterations Based on Dysregulated ceRNA Networks across Cancers |
title_full | Dissecting the Functional Mechanisms of Somatic Copy-Number Alterations Based on Dysregulated ceRNA Networks across Cancers |
title_fullStr | Dissecting the Functional Mechanisms of Somatic Copy-Number Alterations Based on Dysregulated ceRNA Networks across Cancers |
title_full_unstemmed | Dissecting the Functional Mechanisms of Somatic Copy-Number Alterations Based on Dysregulated ceRNA Networks across Cancers |
title_short | Dissecting the Functional Mechanisms of Somatic Copy-Number Alterations Based on Dysregulated ceRNA Networks across Cancers |
title_sort | dissecting the functional mechanisms of somatic copy-number alterations based on dysregulated cerna networks across cancers |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358224/ https://www.ncbi.nlm.nih.gov/pubmed/32668393 http://dx.doi.org/10.1016/j.omtn.2020.06.012 |
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