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Dysregulated gene expression in colorectal cancer upon exposure to bisphenol A alternatives - a new approach

datacite.subject.fosCiências Médicas::Ciências da Saúde
datacite.subject.sdg03:Saúde de Qualidade
dc.contributor.authorLacerda, Rafaela
dc.contributor.authorVentura, Célia
dc.contributor.authorLouro, Henriqueta
dc.contributor.authorSilva, Maria João
dc.contributor.authorRomão, Luísa
dc.date.accessioned2026-02-04T16:23:05Z
dc.date.available2026-02-04T16:23:05Z
dc.date.issued2025-05-12
dc.description.abstractBisphenol A (BPA) has been widely used in plastics and resins since the 1950s, making it a common part of everyday products like food containers and bottle linings. Alternative substances are increasingly replacing BPA, but they are raising health and environmental concerns. Some mimic BPA’s endocrine-disrupting effects, while others affect different biological pathways. Substitutions in bisphenols can alter their biological properties, including nuclear receptor activation. Some BPA alternatives, like BPS, BPF and BPZ, may also pose cancer risks by activating oestrogen receptors, potentially even more than BPA itself. They may also contribute to colorectal cancer (CRC). Research suggests that BPA and its substitutes can influence cancer progression by altering cellular pathways, promoting metastasis and affecting gene expression. One of the key steps in gene expression regulation is translation initiation, whose canonical pathway is globally impaired under stress conditions, like exposure to BPA alternatives. Thus, we will subject NCM460 (normal intestinal mucosa) and HCT116 (colorectal carcinoma) cells to BPS, BPF and BPZ exposure and identify the transcripts actively being translated in such conditions, using ribosome profiling. We will analyse data with the R package anota2seq and evaluate the positively identified targets (compared to total RNA sequencing) for the existence of alternative mechanisms of translation initiation regulating their expression. The accurate characterisation of such mechanisms will be crucial for designing antisense RNA oligomers (ASOs) for potential therapeutic approaches. We will evaluate the cytotoxic effects of BPS, BPF and BPZ in the presence or absence of the selected alternatively translated transcripts (functional or targeted with the designed ASOs). Cytotoxic effects will be assessed through in vitro assays, analysing metabolic activity, membrane integrity, and cell proliferation. Thus, our research explores protein synthesis dysregulation to reduce CRC risks from BPS, BPF and BPZ exposure — an emerging public health issue.eng
dc.description.sponsorshipThis work was carried out in the framework of the European Partnership for the Assessment of Risks from Chemicals (PARC) and has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014.
dc.identifier.urihttp://hdl.handle.net/10400.18/10809
dc.language.isoeng
dc.peerreviewedyes
dc.relationPartnership for the Assessment of Risks from Chemicals
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectPARC
dc.subjectColecteral Cancer
dc.subjectBisphenol A
dc.subjectDysregulation of Gene Expression
dc.subjectGenómica Funcional
dc.subjectGenómica Funcional e Estrutural
dc.titleDysregulated gene expression in colorectal cancer upon exposure to bisphenol A alternatives - a new approacheng
dc.typeconference object
dspace.entity.typePublication
oaire.awardNumber101057014
oaire.awardTitlePartnership for the Assessment of Risks from Chemicals
oaire.awardURIhttp://hdl.handle.net/10400.18/10776
oaire.citation.conferenceDate2025-05-12
oaire.citation.conferencePlaceOslo, Norway
oaire.citation.titlePartnership for the Assessment of Risks from Chemicals (PARC) WP5 Annual Meeting, 12-14 may 2025
oaire.fundingStreamHORIZON Programme Cofund Actions
oaire.versionhttp://purl.org/coar/version/c_b1a7d7d4d402bcce
relation.isProjectOfPublication87519d63-05e5-4a7a-9a69-893088bf7517
relation.isProjectOfPublication.latestForDiscovery87519d63-05e5-4a7a-9a69-893088bf7517

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