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dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional
dc.contributor.advisorUmaña Pérez, Yadi Adriana
dc.contributor.authorLópez González, David Alejandro
dc.date.accessioned2021-10-27T14:11:50Z
dc.date.available2021-10-27T14:11:50Z
dc.date.issued2021-07-28
dc.identifier.urihttps://repositorio.unal.edu.co/handle/unal/80620
dc.descriptionilustraciones, gráficas, tablas
dc.description.abstractEl proceso de implantación placentaria depende de una minuciosa regulación de la invasión de la decidua materna por parte del subtipo celular denominado trofoblasto extravelloso, la evasión del sistema inmune de la madre y la remodelación de la vasculatura local. Estos y otros procesos hacen que la implantación placentaria sea notablemente similar a la invasión tumoral. Las células de cáncer deben su origen a una pérdida de la identidad celular somática acompañada del desarrollo de un fenotipo aberrante que se alcanza como consecuencia de la reactivación de programas de desarrollo embrionario. Se cree que la pérdida de la identidad celular, así como la reactivación de los programas de desarrollo se deben en gran medida a una pérdida de la estabilidad genómica, que a su vez depende del panorama de metilación a nivel genómico. Se sabe que diversos estímulos extracelulares son capaces de promover una remodelación del panorama de metilación de células somáticas tal que contribuye a una transición maligna hacia un fenotipo altamente proliferativo e invasivo, que se debe tanto a la activación estocástica de oncogenes, como a un silenciamiento de genes supresores de tumores. Utilizando la línea celular derivada de trofoblasto, HTR-8/SVneo, por su fenotipo pseudomaligno y como modelo para el estudio de la biología placentaria y de la progresión tumoral, el propósito de este trabajo fue analizar la respuesta funcional de la línea ante un estímulo mitogénico con el péptido IGF2, y determinar cómo esta respuesta se relaciona con la variación en el panorama de metilación genómico y la expresión de RNA mensajero. A través de la interrogación del panorama de metilación genómico y la actividad transcripcional de la línea celular se identificaron variaciones que aparecen por efecto del estímulo y que ocurren de manera simultánea con un aumento de la actividad proliferativa, migratoria e invasiva de la línea celular. Muchos de los genes comprometidos en estas variaciones han sido descritos previamente en cáncer y más aún, hacen parte de vías de señalización a través de las cuales podría estar procediendo el estímulo con IGF2 y que además, son importantes para la adquisición de un fenotipo maligno en diversos tipos de cáncer. En conclusión, el péptido IGF2 tiene la capacidad de aumentar la actividad proliferativa, migratoria e invasiva de la línea celular, y estos cambios ocurren de manera paralela, y probablemente como consecuencia de alteraciones a nivel epigenético y transcripcional. (Texto tomado de la fuente)
dc.description.abstractThe process of placental implantation depends on a thorough regulation of the invasion of the maternal decidua by the cellular subtype known as extravillous trophoblast, invasion of the maternal immune system and remodeling of the local vasculature. These and other processes make the placental implantation remarkably similar to tumor invasion. Cancer cells owe their origin to a loss of somatic cellular identity, accompanied by the development of an aberrant phenotype achieved as a consequence of the stochastic reactivation of embryonic development programs. It is believed that this loss of cellular identity, as well as the reactivation of these programs is owed to a great extent to a loss of genomic stability, which in turn depends on the DNA methylation landscape at the genomic level. It has been observed that extracellular stimuli of diverse kinds are capable of promoting a remodeling of the DNA methylation landscape in somatic cell such that it contributes to a malignant transformation to a highly proliferative, migratory and invasive phenotype, which is owed both to a stochastic activation of oncogenes and a silencing of tumor-repressor genes. Using trophoblast-derived HTR-8/SVneo cell line because its pseudo malignant phenotype and as model for the study of placental biology and tumor progression, the purpose of this work was to analyze the functional response of the cell line as a response to a mitogenic stimulus with IGF2, and to determine how this response is related to the variation of the methylation landscape and the transcriptional activity of the cell line. Through interrogation of the genomic methylation landscape and the transcriptional activity of the cell line, some alterations were identified that appear as a consequence of the stimulus and that occur simultaneously with an increase of the proliferative, migratory and invasive activity of the cell line. Many of the genes compromised in these alterations have been previously described in cancer and moreover, take part in signaling pathways through which the IGF2 stimulus could be proceeding and that are important for the acquisition of a malignant phenotype in several types of cancer. In conclusion, IGF2 peptide has the capacity of promoting the proliferative, migratory and invasive capacities of the cell line and these changes happen simultaneously, and probably as a consequence of alterations at epigenetic and transcriptional levels.
dc.format.extentviii, 62 páginas
dc.format.mimetypeapplication/pdf
dc.language.isospa
dc.publisherUniversidad Nacional de Colombia
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/
dc.subject.ddc570 - Biología::572 - Bioquímica
dc.titleEfecto de IGF2 sobre el panorama de metilación del ADN y la expresión de ARNm asociada en la línea celular HTR-8/SVneo
dc.typeTrabajo de grado - Maestría
dc.type.driverinfo:eu-repo/semantics/masterThesis
dc.type.versioninfo:eu-repo/semantics/acceptedVersion
dc.publisher.programBogotá - Ciencias - Maestría en Ciencias - Bioquímica
dc.contributor.researchgroupGrupo de Investigación en Hormonas
dc.description.degreelevelMaestría
dc.description.degreenameMagíster en Ciencias - Bioquímica
dc.description.researchareaFactores de crecimiento, diferenciación y cáncer
dc.identifier.instnameUniversidad Nacional de Colombia
dc.identifier.reponameRepositorio Institucional Universidad Nacional de Colombia
dc.identifier.repourlhttps://repositorio.unal.edu.co/
dc.publisher.departmentDepartamento de Química
dc.publisher.facultyFacultad de Ciencias
dc.publisher.placeBogotá, Colombia
dc.publisher.branchUniversidad Nacional de Colombia - Sede Bogotá
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dc.rights.accessrightsinfo:eu-repo/semantics/openAccess
dc.subject.decsOncogenes
dc.subject.decsOncogenes
dc.subject.decsMetilación de ADN
dc.subject.decsDNA Methylation
dc.subject.decsReceptor IGF Tipo 2
dc.subject.decsReceptor, IGF Type 2
dc.subject.proposalCáncer
dc.subject.proposalMetilación del DNA
dc.subject.proposalPlacenta
dc.subject.proposalFactor de crecimiento
dc.subject.proposalEpigenética
dc.subject.proposalCancer
dc.subject.proposalIGF signaling system
dc.subject.proposalEpigenetics
dc.subject.proposalGenomic instability
dc.subject.proposalGenic expression
dc.subject.proposalMalignant transformation
dc.title.translatedEffect of IGF2 on the DNA methylation landscape and associated mRNA expression in HTR-8/SVneo cell line
dc.type.coarhttp://purl.org/coar/resource_type/c_bdcc
dc.type.coarversionhttp://purl.org/coar/version/c_ab4af688f83e57aa
dc.type.contentText
dc.type.redcolhttp://purl.org/redcol/resource_type/TM
oaire.accessrightshttp://purl.org/coar/access_right/c_abf2
oaire.fundernameMinisterio de Ciencia, Tecnología e Innovación
dcterms.audience.professionaldevelopmentInvestigadores
dcterms.audience.professionaldevelopmentPúblico general


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