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dc.contributor.authorElhasnaoui, Jamal
dc.contributor.authorFerrero, Giulio
dc.contributor.authorMiano, Valentina
dc.contributor.authorCutrupi, Santina
dc.contributor.authorDe Bortoli, Michele
dc.date.accessioned2022-01-05T10:48:33Z
dc.date.available2022-01-05T10:48:33Z
dc.date.issued2021-12-13
dc.identifier.issn2072-6694
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/332000
dc.description.abstractBACKGROUND: The transcriptional activity of estrogen receptor α (ERα) in breast cancer (BC) is extensively characterized. Our group has previously shown that ERα controls the expression of a number of genes in its unliganded form (apoERα), among which a large group of RNA-binding proteins (RBPs) encode genes, suggesting its role in the control of co- and post-transcriptional events. METHODS: apoERα-mediated RNA processing events were characterized by the analysis of transcript usage and alternative splicing changes in an RNA-sequencing dataset from MCF-7 cells after siRNA-induced ERα downregulation. RESULTS: ApoERα depletion induced an expression change of 681 RBPs, including 84 splicing factors involved in translation, ribonucleoprotein complex assembly, and 3'end processing. ApoERα depletion results in 758 isoform switching events with effects on 3'end length and the splicing of alternative cassette exons. The functional enrichment of these events shows that post-transcriptional regulation is part of the mechanisms by which apoERα controls epithelial-to-mesenchymal transition and BC cell proliferation. In primary BCs, the inclusion levels of the experimentally identified alternatively spliced exons are associated with overall and disease-free survival. CONCLUSION: Our data supports the role of apoERα in maintaining the luminal phenotype of BC cells by extensively regulating gene expression at the alternative splicing level.
dc.languageen
dc.publisherMDPI AG
dc.subjectbreast cancer
dc.subjectestrogen receptor
dc.subjectalternative splicing
dc.subjectEMT
dc.subjectsplicing signature
dc.titleThe Estrogen Receptor α Signaling Pathway Controls Alternative Splicing in the Absence of Ligands in Breast Cancer Cells.
dc.typeArticle
dc.date.updated2022-01-05T10:48:32Z
prism.issueIdentifier24
prism.publicationNameCancers (Basel)
prism.volume13
dc.identifier.doi10.17863/CAM.79448
dcterms.dateAccepted2021-12-10
rioxxterms.versionofrecord10.3390/cancers13246261
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidElhasnaoui, Jamal [0000-0001-9311-0417]
dc.contributor.orcidFerrero, Giulio [0000-0002-4580-0680]
dc.contributor.orcidMiano, Valentina [0000-0002-0260-5885]
dc.contributor.orcidDe Bortoli, Michele [0000-0002-6666-9052]
dc.identifier.eissn2072-6694
pubs.funder-project-idItalian Association for Cancer Research (15600)
pubs.funder-project-idFondazione CRT (2017.0823)
pubs.funder-project-idUniversity of Turin (2018 Local Research)
cam.issuedOnline2021-12-13


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