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dc.contributor.author
Riffo Campos, Ángela
dc.contributor.author
Gimeno Valiente, Francisco
dc.contributor.author
Rodríguez, Fernanda Mariel
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dc.contributor.author
Cervantes, Andrés
dc.contributor.author
López Rodas, Gerardo
dc.contributor.author
Franco, Luis
dc.contributor.author
Castillo, Josefa
dc.date.available
2019-10-21T17:44:13Z
dc.date.issued
2018-04
dc.identifier.citation
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
dc.identifier.issn
1949-2553
dc.identifier.uri
http://hdl.handle.net/11336/86645
dc.description.abstract
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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
oncotarget
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
EPIGENETIC
dc.subject
KRAS
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COLORRECTAL
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CANCER
dc.subject.classification
Otras Ciencias de la Salud
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dc.subject.classification
Ciencias de la Salud
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dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
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dc.title
Role of epigenetic factors in the selection of the alternative splicing isoforms of human KRAS in colorectal cancer cell lines
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2019-10-18T18:44:00Z
dc.journal.volume
9
dc.journal.number
29
dc.journal.pagination
20578-20589
dc.journal.pais
Estados Unidos
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dc.journal.ciudad
Buffalo, NY
dc.description.fil
Fil: Riffo Campos, Ángela. Universidad de Valencia; España
dc.description.fil
Fil: Gimeno Valiente, Francisco. Universidad de Valencia; España
dc.description.fil
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
dc.description.fil
Fil: Cervantes, Andrés. Universidad de Valencia; España
dc.description.fil
Fil: López Rodas, Gerardo. Universidad de Valencia; España
dc.description.fil
Fil: Franco, Luis. Universidad de Valencia; España
dc.description.fil
Fil: Castillo, Josefa. Universidad de Valencia; España
dc.journal.title
Oncotarget
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5945503/
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.oncotarget.com/index.php?journal=oncotarget&page=issue&op=archive
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