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Allele-specific miRNA-binding analysis identifies candidate target genes for breast cancer risk

2020Journal article Open Access
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dc.contributor.authorJacinta-Fernandes, Ana
dc.contributor.authorXavier, Joana M.
dc.contributor.authorMagno, Ramiro
dc.contributor.authorLage, Joel
dc.contributor.authorMaia, Ana-Teresa
dc.date.accessioned2020-03-13T14:57:03Z
dc.date.available2020-03-13T14:57:03Z
dc.date.issued2020
dc.description.abstractMost breast cancer (BC) risk-associated single-nucleotide polymorphisms (raSNPs) identified in genome-wide association studies (GWAS) are believed to cis-regulate the expression of genes. We hypothesise that cis-regulatory variants contributing to disease risk may be affecting microRNA (miRNA) genes and/or miRNA binding. To test this, we adapted two miRNA-binding prediction algorithms-TargetScan and miRanda-to perform allele-specific queries, and integrated differential allelic expression (DAE) and expression quantitative trait loci (eQTL) data, to query 150 genome-wide significant ( P≤5×10-8 ) raSNPs, plus proxies. We found that no raSNP mapped to a miRNA gene, suggesting that altered miRNA targeting is an unlikely mechanism involved in BC risk. Also, 11.5% (6 out of 52) raSNPs located in 3'-untranslated regions of putative miRNA target genes were predicted to alter miRNA::mRNA (messenger RNA) pair binding stability in five candidate target genes. Of these, we propose RNF115, at locus 1q21.1, as a strong novel target gene associated with BC risk, and reinforce the role of miRNA-mediated cis-regulation at locus 19p13.11. We believe that integrating allele-specific querying in miRNA-binding prediction, and data supporting cis-regulation of expression, improves the identification of candidate target genes in BC risk, as well as in other common cancers and complex diseases.pt_PT
dc.description.sponsorshipFunding Agency Portuguese Foundation for Science and Technology CRESC ALGARVE 2020 European Union (EU) 303745 Maratona da Saude Award DL 57/2016/CP1361/CT0042 SFRH/BPD/99502/2014 CBMR-UID/BIM/04773/2013 POCI-01-0145-FEDER-022184pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doihttps://doi.org/10.1038/s41525-019-0112-9pt_PT
dc.identifier.issn2056-7944
dc.identifier.urihttp://hdl.handle.net/10400.1/13592
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherSpringer Naturept_PT
dc.relationGenetic Control of Gene Expression in Cancer Risk
dc.relation.publisherversionhttps://www.nature.com/articles/s41525-019-0112-9pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectData miningpt_PT
dc.subjectRisk factorspt_PT
dc.subjectBreast cancerpt_PT
dc.titleAllele-specific miRNA-binding analysis identifies candidate target genes for breast cancer riskpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleGenetic Control of Gene Expression in Cancer Risk
oaire.awardURIinfo:eu-repo/grantAgreement/EC/FP7/303745/EU
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FBIM%2F04773%2F2013/PT
oaire.citation.issue1pt_PT
oaire.citation.startPage4pt_PT
oaire.citation.titleNPJ Genomic Medicinept_PT
oaire.citation.volume5pt_PT
oaire.fundingStreamFP7
oaire.fundingStream5876
person.familyNameJacinta-Fernandes
person.familyNameGonçalves de Gouveia Maia Xavier
person.familyNameMagno
person.familyNameLage
person.familyNameMaia
person.givenNameAna
person.givenNameJoana
person.givenNameRamiro
person.givenNameJoel
person.givenNameAna-Teresa
person.identifier1489493
person.identifier.ciencia-idEE13-176A-5613
person.identifier.orcid0000-0002-0021-9702
person.identifier.orcid0000-0002-0702-6700
person.identifier.orcid0000-0001-5226-3441
person.identifier.orcid0000-0002-2789-8303
person.identifier.orcid0000-0002-0454-9207
person.identifier.ridI-4676-2014
person.identifier.ridF-4404-2012
person.identifier.scopus-author-id36061472900
person.identifier.scopus-author-id14319300100
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameEuropean Commission
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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