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Mutation-class dependent signatures outweigh disease-associated processes in cystic fibrosis cells

BACKGROUND: The phenotypic heterogeneity observed in Cystic Fibrosis (CF) patients suggests the involvement of other genes, besides CFTR. Here, we combined transcriptome and proteome analysis to understand the global gene expression patterns associated with five prototypical CFTR mutations. RESULTS:...

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Autores principales: Santos, Lúcia, Nascimento, Rui, Duarte, Aires, Railean, Violeta, Amaral, Margarida D., Harrison, Patrick T., Gama-Carvalho, Margarida, Farinha, Carlos M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9912517/
https://www.ncbi.nlm.nih.gov/pubmed/36759923
http://dx.doi.org/10.1186/s13578-023-00975-y
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author Santos, Lúcia
Nascimento, Rui
Duarte, Aires
Railean, Violeta
Amaral, Margarida D.
Harrison, Patrick T.
Gama-Carvalho, Margarida
Farinha, Carlos M.
author_facet Santos, Lúcia
Nascimento, Rui
Duarte, Aires
Railean, Violeta
Amaral, Margarida D.
Harrison, Patrick T.
Gama-Carvalho, Margarida
Farinha, Carlos M.
author_sort Santos, Lúcia
collection PubMed
description BACKGROUND: The phenotypic heterogeneity observed in Cystic Fibrosis (CF) patients suggests the involvement of other genes, besides CFTR. Here, we combined transcriptome and proteome analysis to understand the global gene expression patterns associated with five prototypical CFTR mutations. RESULTS: Evaluation of differentially expressed genes and proteins unveiled common and mutation-specific changes revealing functional signatures that are much more associated with the specific molecular defects associated with each mutation than to the CFTR loss-of-function phenotype. The combination of both datasets revealed that mutation-specific detected translated-transcripts (Dtt) have a high level of consistency. CONCLUSIONS: This is the first combined transcriptomic and proteomic study focusing on prototypical CFTR mutations. Analysis of Dtt provides novel insight into the pathophysiology of CF, and the mechanisms through which each mutation class causes disease and will likely contribute to the identification of new therapeutic targets and/or biomarkers for CF. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13578-023-00975-y.
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spelling pubmed-99125172023-02-11 Mutation-class dependent signatures outweigh disease-associated processes in cystic fibrosis cells Santos, Lúcia Nascimento, Rui Duarte, Aires Railean, Violeta Amaral, Margarida D. Harrison, Patrick T. Gama-Carvalho, Margarida Farinha, Carlos M. Cell Biosci Research BACKGROUND: The phenotypic heterogeneity observed in Cystic Fibrosis (CF) patients suggests the involvement of other genes, besides CFTR. Here, we combined transcriptome and proteome analysis to understand the global gene expression patterns associated with five prototypical CFTR mutations. RESULTS: Evaluation of differentially expressed genes and proteins unveiled common and mutation-specific changes revealing functional signatures that are much more associated with the specific molecular defects associated with each mutation than to the CFTR loss-of-function phenotype. The combination of both datasets revealed that mutation-specific detected translated-transcripts (Dtt) have a high level of consistency. CONCLUSIONS: This is the first combined transcriptomic and proteomic study focusing on prototypical CFTR mutations. Analysis of Dtt provides novel insight into the pathophysiology of CF, and the mechanisms through which each mutation class causes disease and will likely contribute to the identification of new therapeutic targets and/or biomarkers for CF. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13578-023-00975-y. BioMed Central 2023-02-09 /pmc/articles/PMC9912517/ /pubmed/36759923 http://dx.doi.org/10.1186/s13578-023-00975-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Santos, Lúcia
Nascimento, Rui
Duarte, Aires
Railean, Violeta
Amaral, Margarida D.
Harrison, Patrick T.
Gama-Carvalho, Margarida
Farinha, Carlos M.
Mutation-class dependent signatures outweigh disease-associated processes in cystic fibrosis cells
title Mutation-class dependent signatures outweigh disease-associated processes in cystic fibrosis cells
title_full Mutation-class dependent signatures outweigh disease-associated processes in cystic fibrosis cells
title_fullStr Mutation-class dependent signatures outweigh disease-associated processes in cystic fibrosis cells
title_full_unstemmed Mutation-class dependent signatures outweigh disease-associated processes in cystic fibrosis cells
title_short Mutation-class dependent signatures outweigh disease-associated processes in cystic fibrosis cells
title_sort mutation-class dependent signatures outweigh disease-associated processes in cystic fibrosis cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9912517/
https://www.ncbi.nlm.nih.gov/pubmed/36759923
http://dx.doi.org/10.1186/s13578-023-00975-y
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