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Regulation of the alternative splicing of RAC1B in tumor cells

2023Master thesis Restricted access
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dc.contributor.advisorGonçalves, Vânia
dc.contributor.advisorJordan, Peter
dc.contributor.authorBizarro, Inês
dc.date.accessioned2024-03-07T18:20:54Z
dc.date.embargo2025-10-26
dc.date.issued2023
dc.descriptionDissertação de mestrado em Bioquímica e Biomedicina, apresentada à Faculdade de Ciências da Universidade de Lisboa, 2023.pt_PT
dc.descriptionDissertação orientada por: Doutora Vânia Gonçalves e Doutor Peter Jordan.pt_PT
dc.descriptionTrabalho de dissertação de Mestrado realizado no Laboratório de Oncobiologia e Vias de Sinalização do Instituto Nacional de Saúde Doutor Ricardo Jorge.pt_PT
dc.description.abstractCancer is a molecularly heterogeneous disease that presents genetic modifications in different alternative pathways. Namely, a subgroup of colorectal cancer (CRC) is characterized by the simultaneous presence of an oncogenic mutation in BRAF and overexpression of RAC1B, an alternative splicing variant of the small GTPase RAC1. Together, these two changes stimulate signalling pathways that induce the proliferation and survival of CRC cells. Previously, the splicing factors (SFs) ESRP1 and SRSF1 were reported to promote RAC1B overexpression in this type of tumor, while SRSF3 inhibited it. However, the overexpression of RAC1B has also been identified in breast and lung tumors. As such, this work aimed to study the modulatory role of ESRP1, SRSF1 and SRSF3 on RAC1B alternative splicing in breast and lung cancer cells, using CRC cells as an experimental control since the role of these SFs has already been documented in these types of tumor. The SFs were overexpressed in the cells by co-transfection with a RAC1 minigene and the expression levels of the minigene-derived transcripts were analysed by RT-PCR. Next, the SFs endogenous expression was depleted by siRNA transfection and the endogenous levels of RAC1B transcript and protein were assessed through RT-PCR and Western blot, respectively. The obtained results indicate a role for SRSF1 and SRSF3 in positively and negatively modulating RAC1B alternative splicing, respectively, in both breast and lung cancer cells, as previously described for CRC. Intriguingly, ESRP1 inhibited RAC1B alternative splicing in these cells, revealing an opposite role to what was previously observed for CRC. Although future studies should be performed to confirm these results, ESRP1 and SRSF3 act as inhibitors of RAC1B alternative splicing whereas SRSF1 acts as an enhancer, in both breast and lung cancer cells.pt_PT
dc.description.abstractO foco deste trabalho experimental consistiu em averiguar se os fatores de splicing ESRP1, SRSF1 e SRSF3 desempenham um efeito modulatório no splicing alternativo de RAC1B em tumores da mama e do pulmão, nos quais a sua atividade já foi reportada.pt_PT
dc.description.sponsorshipFunding: Bolsa de Iniciação à Investigação do Biosystems and Integrative Sciences Institute no âmbito do BioISI Junior Programe 2022 (UIDP/04046/2020) financiada pela Fundação para a Ciência e Tecnologiapt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.urihttp://hdl.handle.net/10400.18/9162
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.relationBiosystems and Integrative Sciences Institute
dc.relation.publisherversionhttps://repositorio.ul.pt/handle/10451/62714pt_PT
dc.subjectCancerpt_PT
dc.subjectAlternative Splicingpt_PT
dc.subjectRAC1Bpt_PT
dc.subjectTumorigenesispt_PT
dc.subjectSplicing Factorspt_PT
dc.subjectCancropt_PT
dc.subjectSplicing Alternativopt_PT
dc.subjectTumorigénesept_PT
dc.subjectFatores de Splicingpt_PT
dc.subjectVias de Transdução de Sinal e Patologias Associadaspt_PT
dc.titleRegulation of the alternative splicing of RAC1B in tumor cellspt_PT
dc.typemaster thesis
dspace.entity.typePublication
oaire.awardTitleBiosystems and Integrative Sciences Institute
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F04046%2F2020/PT
oaire.citation.conferencePlaceLisboa, Portugalpt_PT
oaire.citation.endPage42pt_PT
oaire.citation.startPagex,1pt_PT
oaire.fundingStream6817 - DCRRNI ID
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.embargofctAcesso de acordo com https://repositorio.ul.pt/pt_PT
rcaap.rightsembargoedAccesspt_PT
rcaap.typemasterThesispt_PT
relation.isProjectOfPublicatione8390b4d-1833-4925-a0ab-5fff0527efaa
relation.isProjectOfPublication.latestForDiscoverye8390b4d-1833-4925-a0ab-5fff0527efaa

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