Repository logo
 
Publication

Identification of mTOR and AGO1 IRES trans-acting factors

2020-11-20Conference object Restricted access
Simple item page
dc.contributor.authorMarques, Rita
dc.contributor.authorLacerda, Rafaela
dc.contributor.authorRomão, Luísa
dc.date.accessioned2021-03-13T17:00:35Z
dc.date.embargo2025-12-31
dc.date.issued2020-11-20
dc.description.abstractCancer is the second leading cause of death globally; therefore, its study is crucial to discover new therapies. Under stress, the regular process of protein synthesis (canonical translation) is impaired, while a back-up mechanism mediated by internal ribosome entry sites (IRES) continues to function, allowing the synthesis of proteins that maintain cellular viability. This also happens in cancer cells, contributing for their survival and consequent tumorigenesis. IRES-mediated translation and its regulation by IRES trans-acting factors (ITAFs) has been correlated to metastasis and chemotherapeutic drug resistance. Therefore, our main goal was to validate ITAFs and assess their significance in cancer onset, thus becoming candidates as novel therapeutic targets. A bicistronic reporter system, which contains a first cistron translated via canonical translation and a second one translated by IRES of mTOR1 and AGO12 was used to test IRES-driven translation initiation activity. Experiments were carried out in which several proteins (hnRNPs) were silenced by specific siRNAs to analyse their function as ITAFs of mTOR and AGO1 IRESs. Also, distinct drugs were applied to simulate endoplasmic reticulum (ER) or hypoxia stress, to evaluate their effect on IRES activity. The relative IRES activity was assessed by luminescence tests and the protein levels by Western blot. In general, knockdown of hnRNPK and hnRNPU seems to decrease the IRES activity by ~60% and ~30% respectively, while hnRNPC knockdown does not show a significant effect. Regarding the ER stress, hnRNPK knockdown seems to decrease even more the IRES activity, while hnRNPU depletion induces a significant increase. On the other hand, in hypoxia, the hnRNPs knockdowns do not significantly affect IRES activity. These results indicate that hnRNPK and hnRNPU may function as ITAFs of mTOR and AGO1 IRES activity in cells under ER stress. Our data can be decisive for a better understanding of carcinogenesis and suggest new therapeutic targets for cancer treatment. 1. Marques-Ramos, A., et.al. 2017. RNA. 23, 1712-1728 2. Lacerda, R. 2016. Faculdade de Ciências e Tecnologia da Universidade NOVA de Lisboapt_PT
dc.description.sponsorshipWork partially supported by UID/MULTI/04046/2019 Research Unit grant from FCT, Portugal (to BioISI)pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.urihttp://hdl.handle.net/10400.18/7466
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.subjectCancerpt_PT
dc.subjectmTORpt_PT
dc.subjectAGO1 IRESpt_PT
dc.subjectDoenças Genéticaspt_PT
dc.subjectGenómica Funcional e Estruturalpt_PT
dc.titleIdentification of mTOR and AGO1 IRES trans-acting factorspt_PT
dc.typeconference object
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FMulti%2F04046%2F2013/PT (2019)
oaire.citation.conferencePlaceLisboa, Portugal (online)pt_PT
oaire.citation.title24ª Reunião Científica da Sociedade Portuguesa de Genética Humana, 20 novembro 2020pt_PT
oaire.fundingStream5876
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsembargoedAccesspt_PT
rcaap.typeconferenceObjectpt_PT
relation.isProjectOfPublication0dbd968f-ea65-4a2a-9b40-008aff7adbeb
relation.isProjectOfPublication.latestForDiscovery0dbd968f-ea65-4a2a-9b40-008aff7adbeb

Files

Original bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
poster Rita SPGH 2020.pdf
Size:
1.09 MB
Format:
Adobe Portable Document Format
Download

Collections

DGH - Posters/abstracts em congressos internacionais