The contribution of tRNA pool deregulation in the acquisition of a malignant phenotype

Detalhes bibliográficos
Autor(a) principal: Fidalgo,Ana Patrícia Figueiredo
Data de Publicação: 2015
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10773/15506
Resumo: Human tissues display different tRNA expression patterns correlated with the codon usage of highly-expressed genes, which may represent a form of translational control since tRNAs are critical players during protein synthesis. In cancer cells, misregulation of the components of translational machinery is observed, namely elevated levels of tRNAs in a specific fashion, correlated with a preferential expression of cancer-related genes. Therefore, tRNA pool deregulation may enhance the translational efficiency of these genes, promoting the malignant transformation. The tumorigenic process is accompanied by increased cellular protein load. Evasion of apoptosis, genome instability and frequent mutations are also observed in cancer cells. This may promote accumulation of mutated proteins that leads to proteotoxic stress and high production of HSPs, in order to counteract protein instability. Furthermore, high levels of misfolded proteins derived from the high rate of protein synthesis induce other protein quality control pathways to support the action of chaperones: the unfolded protein response and the endoplasmic reticulum-associated degradation system. This study aimed to evaluate the influence of tRNA pool deregulation in the acquisition of a malignant phenotype and the contribution of protein quality control pathways in cell transformation. In general, the results showed that the deregulation of the tRNA pool prompted by tRNASer overexpression leads to the acquisition of an intermediary phenotype between normal cells and cancer cells. Therefore, we concluded that this deregulation may be a driven force for cellular malignancy.
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spelling The contribution of tRNA pool deregulation in the acquisition of a malignant phenotypeBiologia molecular e celularTecidos (Biologia) - PatologiaÁcido ribonucleicoProteínas - Síntese químicaHuman tissues display different tRNA expression patterns correlated with the codon usage of highly-expressed genes, which may represent a form of translational control since tRNAs are critical players during protein synthesis. In cancer cells, misregulation of the components of translational machinery is observed, namely elevated levels of tRNAs in a specific fashion, correlated with a preferential expression of cancer-related genes. Therefore, tRNA pool deregulation may enhance the translational efficiency of these genes, promoting the malignant transformation. The tumorigenic process is accompanied by increased cellular protein load. Evasion of apoptosis, genome instability and frequent mutations are also observed in cancer cells. This may promote accumulation of mutated proteins that leads to proteotoxic stress and high production of HSPs, in order to counteract protein instability. Furthermore, high levels of misfolded proteins derived from the high rate of protein synthesis induce other protein quality control pathways to support the action of chaperones: the unfolded protein response and the endoplasmic reticulum-associated degradation system. This study aimed to evaluate the influence of tRNA pool deregulation in the acquisition of a malignant phenotype and the contribution of protein quality control pathways in cell transformation. In general, the results showed that the deregulation of the tRNA pool prompted by tRNASer overexpression leads to the acquisition of an intermediary phenotype between normal cells and cancer cells. Therefore, we concluded that this deregulation may be a driven force for cellular malignancy.Os tecidos humanos exibem diferentes padrões de expressão de tRNAs que se correlacionam com o codon usage de genes altamente expressos. Isto pode representar um controlo ao nível da tradução tendo em conta que os tRNAs são intervenientes importantes durante a síntese proteica. Nas células cancerígenas é observada a desregulação de componentes do processo de tradução, sendo que elevados níveis de tRNAs específicos estão correlacionados com a expressão preferencial de genes relacionados com o cancro. Assim, a desregulação da pool de tRNAs pode aumentar a eficiência de tradução desses genes, promovendo a transformação maligna. O processo tumorigénico é acompanhado por aumento do conteúdo proteico celular. A evasão à apoptose, a instabilidade do genoma e as mutações frequentes são também observadas em células cancerígenas. Isto pode promover a acumulação de proteínas mutantes que desencadeia o stress proteotóxico e a produção elevada de HSPs, de forma a contrariar a instabilidade proteica. Para além disso, elevados níveis de proteínas incorretamente enoveladas, derivadas da elevada taxa de síntese proteica, induzem outras vias de controlo de qualidade proteica que auxiliam a ação dos chaperones: a resposta das proteínas não enoveladas e o sistema de degradação associado ao retículo endoplasmático. Este estudo teve como objetivo avaliar a influência da desregulação da pool de tRNAs na aquisição do fenótipo maligno e a contribuição das vias de controlo de qualidade proteica na transformação celular. Globalmente, os resultados mostraram que a desregulação da pool de tRNAs induzida pela sobre expressão do tRNASer leva à aquisição de um fenótipo intermédio entre as células normais e as células cancerígenas. Assim, concluímos que esta desregulação pode representar um promotor da aquisição da malignidade celular.Universidade de Aveiro2018-07-20T14:00:53Z2015-12-16T00:00:00Z2015-12-162017-12-09T16:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10773/15506TID:201564068engFidalgo,Ana Patrícia Figueiredoinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-02-22T11:28:42Zoai:ria.ua.pt:10773/15506Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T02:50:52.800300Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv The contribution of tRNA pool deregulation in the acquisition of a malignant phenotype
title The contribution of tRNA pool deregulation in the acquisition of a malignant phenotype
spellingShingle The contribution of tRNA pool deregulation in the acquisition of a malignant phenotype
Fidalgo,Ana Patrícia Figueiredo
Biologia molecular e celular
Tecidos (Biologia) - Patologia
Ácido ribonucleico
Proteínas - Síntese química
title_short The contribution of tRNA pool deregulation in the acquisition of a malignant phenotype
title_full The contribution of tRNA pool deregulation in the acquisition of a malignant phenotype
title_fullStr The contribution of tRNA pool deregulation in the acquisition of a malignant phenotype
title_full_unstemmed The contribution of tRNA pool deregulation in the acquisition of a malignant phenotype
title_sort The contribution of tRNA pool deregulation in the acquisition of a malignant phenotype
author Fidalgo,Ana Patrícia Figueiredo
author_facet Fidalgo,Ana Patrícia Figueiredo
author_role author
dc.contributor.author.fl_str_mv Fidalgo,Ana Patrícia Figueiredo
dc.subject.por.fl_str_mv Biologia molecular e celular
Tecidos (Biologia) - Patologia
Ácido ribonucleico
Proteínas - Síntese química
topic Biologia molecular e celular
Tecidos (Biologia) - Patologia
Ácido ribonucleico
Proteínas - Síntese química
description Human tissues display different tRNA expression patterns correlated with the codon usage of highly-expressed genes, which may represent a form of translational control since tRNAs are critical players during protein synthesis. In cancer cells, misregulation of the components of translational machinery is observed, namely elevated levels of tRNAs in a specific fashion, correlated with a preferential expression of cancer-related genes. Therefore, tRNA pool deregulation may enhance the translational efficiency of these genes, promoting the malignant transformation. The tumorigenic process is accompanied by increased cellular protein load. Evasion of apoptosis, genome instability and frequent mutations are also observed in cancer cells. This may promote accumulation of mutated proteins that leads to proteotoxic stress and high production of HSPs, in order to counteract protein instability. Furthermore, high levels of misfolded proteins derived from the high rate of protein synthesis induce other protein quality control pathways to support the action of chaperones: the unfolded protein response and the endoplasmic reticulum-associated degradation system. This study aimed to evaluate the influence of tRNA pool deregulation in the acquisition of a malignant phenotype and the contribution of protein quality control pathways in cell transformation. In general, the results showed that the deregulation of the tRNA pool prompted by tRNASer overexpression leads to the acquisition of an intermediary phenotype between normal cells and cancer cells. Therefore, we concluded that this deregulation may be a driven force for cellular malignancy.
publishDate 2015
dc.date.none.fl_str_mv 2015-12-16T00:00:00Z
2015-12-16
2017-12-09T16:00:00Z
2018-07-20T14:00:53Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10773/15506
TID:201564068
url http://hdl.handle.net/10773/15506
identifier_str_mv TID:201564068
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidade de Aveiro
publisher.none.fl_str_mv Universidade de Aveiro
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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