Role of epigenetic factors in the selection of the alternative splicing isoforms of human KRAS in colorectal cancer cell lines

Autores
Riffo Campos, Ángela; Gimeno Valiente, Francisco; Rodríguez, Fernanda Mariel; Cervantes, Andrés; López Rodas, Gerardo; Franco, Luis; Castillo, Josefa
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Mutation-driven activation of KRAS is crucial to cancer development. The humangene yields four mRNA splicing isoforms, 4A and 4B being translated to protein. Theirdifferent properties and oncogenic potential have been studied, but the mechanismsdeciding the ratio 4A/4B are not known. To address this issue, the expression of thefour KRAS isoforms was determined in 9 human colorectal cancer cell lines. HCT116and SW48 were further selected because they present the highest difference in theratio 4A/4B (twice as much in HCT116 than in SW48). Chromatin structure wasanalysed at the exon 4A, characteristic of isoform 4A, at its intronic borders and at thetwo flanking exons. The low nucleosome occupancy at exon 4A in both cell lines mayresult in a fast transcriptional rate, which would explain the general lower abundanceof isoform 4A, also found in cells and tissues by other authors, but due to its similaritybetween both cell lines, chromatin structure does not influence alternative splicing.DNA methylation downstream exon 4A significantly differs in HCT116 and SW48cells, but the CCCTC-binding factor, which affects the processivity of RNA polymeraseand the alternative splicing, does not bind the differentially methylated sequences.Quantitative epigenetic analysis at mononucleosomal level revealed significantdifferences between both cell lines in H3K4me3, H3K27me3, H3K36me3, H3K9ac,H3K27ac and H4K20me1, and the inhibition of some histone-modifying enzymes altersthe ratio 4A/4B. It can be concluded that the epigenetic modification of histones hasan influence on the selection of isoforms 4A and 4B.
Fil: Riffo Campos, Ángela. Universidad de Valencia; España
Fil: Gimeno Valiente, Francisco. Universidad de Valencia; España
Fil: Rodríguez, Fernanda Mariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; Argentina
Fil: Cervantes, Andrés. Universidad de Valencia; España
Fil: López Rodas, Gerardo. Universidad de Valencia; España
Fil: Franco, Luis. Universidad de Valencia; España
Fil: Castillo, Josefa. Universidad de Valencia; España
Materia
EPIGENETIC
KRAS
COLORRECTAL
CANCER
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/86645
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/86645
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Role of epigenetic factors in the selection of the alternative splicing isoforms of human KRAS in colorectal cancer cell linesRiffo Campos, ÁngelaGimeno Valiente, FranciscoRodríguez, Fernanda MarielCervantes, AndrésLópez Rodas, GerardoFranco, LuisCastillo, JosefaEPIGENETICKRASCOLORRECTALCANCERhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Mutation-driven activation of KRAS is crucial to cancer development. The humangene yields four mRNA splicing isoforms, 4A and 4B being translated to protein. Theirdifferent properties and oncogenic potential have been studied, but the mechanismsdeciding the ratio 4A/4B are not known. To address this issue, the expression of thefour KRAS isoforms was determined in 9 human colorectal cancer cell lines. HCT116and SW48 were further selected because they present the highest difference in theratio 4A/4B (twice as much in HCT116 than in SW48). Chromatin structure wasanalysed at the exon 4A, characteristic of isoform 4A, at its intronic borders and at thetwo flanking exons. The low nucleosome occupancy at exon 4A in both cell lines mayresult in a fast transcriptional rate, which would explain the general lower abundanceof isoform 4A, also found in cells and tissues by other authors, but due to its similaritybetween both cell lines, chromatin structure does not influence alternative splicing.DNA methylation downstream exon 4A significantly differs in HCT116 and SW48cells, but the CCCTC-binding factor, which affects the processivity of RNA polymeraseand the alternative splicing, does not bind the differentially methylated sequences.Quantitative epigenetic analysis at mononucleosomal level revealed significantdifferences between both cell lines in H3K4me3, H3K27me3, H3K36me3, H3K9ac,H3K27ac and H4K20me1, and the inhibition of some histone-modifying enzymes altersthe ratio 4A/4B. It can be concluded that the epigenetic modification of histones hasan influence on the selection of isoforms 4A and 4B.Fil: Riffo Campos, Ángela. Universidad de Valencia; EspañaFil: Gimeno Valiente, Francisco. Universidad de Valencia; EspañaFil: Rodríguez, Fernanda Mariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; ArgentinaFil: Cervantes, Andrés. Universidad de Valencia; EspañaFil: López Rodas, Gerardo. Universidad de Valencia; EspañaFil: Franco, Luis. Universidad de Valencia; EspañaFil: Castillo, Josefa. Universidad de Valencia; Españaoncotarget2018-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/86645Riffo Campos, Ángela; Gimeno Valiente, Francisco; Rodríguez, Fernanda Mariel; Cervantes, Andrés; López Rodas, Gerardo; et al.; Role of epigenetic factors in the selection of the alternative splicing isoforms of human KRAS in colorectal cancer cell lines; oncotarget; Oncotarget; 9; 29; 4-2018; 20578-205891949-2553CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5945503/info:eu-repo/semantics/altIdentifier/url/http://www.oncotarget.com/index.php?journal=oncotarget&page=issue&op=archiveinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:45:29Zoai:ri.conicet.gov.ar:11336/86645instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:45:30.042CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Role of epigenetic factors in the selection of the alternative splicing isoforms of human KRAS in colorectal cancer cell lines
title Role of epigenetic factors in the selection of the alternative splicing isoforms of human KRAS in colorectal cancer cell lines
spellingShingle Role of epigenetic factors in the selection of the alternative splicing isoforms of human KRAS in colorectal cancer cell lines
Riffo Campos, Ángela
EPIGENETIC
KRAS
COLORRECTAL
CANCER
title_short Role of epigenetic factors in the selection of the alternative splicing isoforms of human KRAS in colorectal cancer cell lines
title_full Role of epigenetic factors in the selection of the alternative splicing isoforms of human KRAS in colorectal cancer cell lines
title_fullStr Role of epigenetic factors in the selection of the alternative splicing isoforms of human KRAS in colorectal cancer cell lines
title_full_unstemmed Role of epigenetic factors in the selection of the alternative splicing isoforms of human KRAS in colorectal cancer cell lines
title_sort Role of epigenetic factors in the selection of the alternative splicing isoforms of human KRAS in colorectal cancer cell lines
dc.creator.none.fl_str_mv Riffo Campos, Ángela
Gimeno Valiente, Francisco
Rodríguez, Fernanda Mariel
Cervantes, Andrés
López Rodas, Gerardo
Franco, Luis
Castillo, Josefa
author Riffo Campos, Ángela
author_facet Riffo Campos, Ángela
Gimeno Valiente, Francisco
Rodríguez, Fernanda Mariel
Cervantes, Andrés
López Rodas, Gerardo
Franco, Luis
Castillo, Josefa
author_role author
author2 Gimeno Valiente, Francisco
Rodríguez, Fernanda Mariel
Cervantes, Andrés
López Rodas, Gerardo
Franco, Luis
Castillo, Josefa
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv EPIGENETIC
KRAS
COLORRECTAL
CANCER
topic EPIGENETIC
KRAS
COLORRECTAL
CANCER
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Mutation-driven activation of KRAS is crucial to cancer development. The humangene yields four mRNA splicing isoforms, 4A and 4B being translated to protein. Theirdifferent properties and oncogenic potential have been studied, but the mechanismsdeciding the ratio 4A/4B are not known. To address this issue, the expression of thefour KRAS isoforms was determined in 9 human colorectal cancer cell lines. HCT116and SW48 were further selected because they present the highest difference in theratio 4A/4B (twice as much in HCT116 than in SW48). Chromatin structure wasanalysed at the exon 4A, characteristic of isoform 4A, at its intronic borders and at thetwo flanking exons. The low nucleosome occupancy at exon 4A in both cell lines mayresult in a fast transcriptional rate, which would explain the general lower abundanceof isoform 4A, also found in cells and tissues by other authors, but due to its similaritybetween both cell lines, chromatin structure does not influence alternative splicing.DNA methylation downstream exon 4A significantly differs in HCT116 and SW48cells, but the CCCTC-binding factor, which affects the processivity of RNA polymeraseand the alternative splicing, does not bind the differentially methylated sequences.Quantitative epigenetic analysis at mononucleosomal level revealed significantdifferences between both cell lines in H3K4me3, H3K27me3, H3K36me3, H3K9ac,H3K27ac and H4K20me1, and the inhibition of some histone-modifying enzymes altersthe ratio 4A/4B. It can be concluded that the epigenetic modification of histones hasan influence on the selection of isoforms 4A and 4B.
Fil: Riffo Campos, Ángela. Universidad de Valencia; España
Fil: Gimeno Valiente, Francisco. Universidad de Valencia; España
Fil: Rodríguez, Fernanda Mariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; Argentina
Fil: Cervantes, Andrés. Universidad de Valencia; España
Fil: López Rodas, Gerardo. Universidad de Valencia; España
Fil: Franco, Luis. Universidad de Valencia; España
Fil: Castillo, Josefa. Universidad de Valencia; España
description Mutation-driven activation of KRAS is crucial to cancer development. The humangene yields four mRNA splicing isoforms, 4A and 4B being translated to protein. Theirdifferent properties and oncogenic potential have been studied, but the mechanismsdeciding the ratio 4A/4B are not known. To address this issue, the expression of thefour KRAS isoforms was determined in 9 human colorectal cancer cell lines. HCT116and SW48 were further selected because they present the highest difference in theratio 4A/4B (twice as much in HCT116 than in SW48). Chromatin structure wasanalysed at the exon 4A, characteristic of isoform 4A, at its intronic borders and at thetwo flanking exons. The low nucleosome occupancy at exon 4A in both cell lines mayresult in a fast transcriptional rate, which would explain the general lower abundanceof isoform 4A, also found in cells and tissues by other authors, but due to its similaritybetween both cell lines, chromatin structure does not influence alternative splicing.DNA methylation downstream exon 4A significantly differs in HCT116 and SW48cells, but the CCCTC-binding factor, which affects the processivity of RNA polymeraseand the alternative splicing, does not bind the differentially methylated sequences.Quantitative epigenetic analysis at mononucleosomal level revealed significantdifferences between both cell lines in H3K4me3, H3K27me3, H3K36me3, H3K9ac,H3K27ac and H4K20me1, and the inhibition of some histone-modifying enzymes altersthe ratio 4A/4B. It can be concluded that the epigenetic modification of histones hasan influence on the selection of isoforms 4A and 4B.
publishDate 2018
dc.date.none.fl_str_mv 2018-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/86645
Riffo Campos, Ángela; Gimeno Valiente, Francisco; Rodríguez, Fernanda Mariel; Cervantes, Andrés; López Rodas, Gerardo; et al.; Role of epigenetic factors in the selection of the alternative splicing isoforms of human KRAS in colorectal cancer cell lines; oncotarget; Oncotarget; 9; 29; 4-2018; 20578-20589
1949-2553
CONICET Digital
CONICET
url http://hdl.handle.net/11336/86645
identifier_str_mv Riffo Campos, Ángela; Gimeno Valiente, Francisco; Rodríguez, Fernanda Mariel; Cervantes, Andrés; López Rodas, Gerardo; et al.; Role of epigenetic factors in the selection of the alternative splicing isoforms of human KRAS in colorectal cancer cell lines; oncotarget; Oncotarget; 9; 29; 4-2018; 20578-20589
1949-2553
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5945503/
info:eu-repo/semantics/altIdentifier/url/http://www.oncotarget.com/index.php?journal=oncotarget&page=issue&op=archive
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv oncotarget
publisher.none.fl_str_mv oncotarget
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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