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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...

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Autores principales: Ping, Yanyan, Zhou, Yao, Hu, Jing, Pang, Lin, Xu, Chaohan, Xiao, Yun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2020
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.
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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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