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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorGorbatenko, Andrej
dc.contributor.authorSøkilde, Rolf
dc.contributor.authorSorensen, Ester E.
dc.contributor.authorNewie, Inga
dc.contributor.authorPersson, Helena
dc.contributor.authorMorancho Armisen, Beatriz
dc.contributor.authorArribas López, Joaquin Vicente
dc.date.accessioned2021-04-20T11:30:02Z
dc.date.available2021-04-20T11:30:02Z
dc.date.issued2019-03-04
dc.identifier.citationGorbatenko A, Søkilde R, Sorensen EE, Newie I, Persson H, Morancho B, et al. HER2 and p95HER2 differentially regulate miRNA expression in MCF-7 breast cancer cells and downregulate MYB proteins through miR-221/222 and miR-503. Sci Rep. 2019 Mar 4;9(1):3352.
dc.identifier.issn2045-2322
dc.identifier.urihttp://hdl.handle.net/11351/5878
dc.descriptionDisease Mechanisms; Breast Cancer
dc.description.abstractThe HER2 oncogene and its truncated form p95HER2 play central roles in breast cancer. Here, we show that although HER2 and p95HER2 generally elicit qualitatively similar changes in miRNA profile in MCF-7 breast cancer cells, a subset of changes are distinct and p95HER2 shifts the miRNA profile towards the basal breast cancer subtype. High-throughput miRNA profiling was carried out 15, 36 and 60 h after HER2 or p95HER2 expression and central hits validated by RT-qPCR. miRNAs strongly regulated by p95HER2 yet not by HER2, included miR-221, miR-222, miR-503, miR-29a, miR-149, miR-196 and miR-361. Estrogen receptor-α (ESR1) expression was essentially ablated by p95HER2 expression, in a manner recapitulated by miR-221/-222 mimics. c-Myb family transcription factors MYB and MYBL1, but not MYBL2, were downregulated by p95HER2 and by miR-503 or miR-221/-222 mimics. MYBL1 3′UTR inhibition by miR-221/222 was lost by deletion of a single putative miR-221/222 binding sites. p95HER2 expression, or knockdown of either MYB protein, elicited upregulation of tissue inhibitor of matrix metalloprotease-2 (TIMP2). miR-221/222 and -503 mimics increased, and TIMP2 knockdown decreased, cell migration and invasion. A similar pathway was operational in T47D- and SKBr-3 cells. This work reveals important differences between HER2- and p95HER2- mediated miRNA changes in breast cancer cells, provides novel mechanistic insight into regulation of MYB family transcription factors by p95HER2, and points to a role for a miR-221/222– MYB family–TIMP2 axis in regulation of motility in breast cancer cells.
dc.language.isoeng
dc.publisherNature Publishing Group
dc.relation.ispartofseriesScientific Reports;9(1)
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceScientia
dc.subjectMama - Càncer
dc.subjectCèl·lules canceroses
dc.subject.meshBreast Neoplasms
dc.subject.meshMCF-7 Cells
dc.titleHER2 and p95HER2 differentially regulate miRNA expression in MCF-7 breast cancer cells and downregulate MYB proteins through miR-221/222 and miR-503
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1038/s41598-019-39733-x
dc.subject.decsneoplasias de la mama
dc.subject.decscélulas MCF-7
dc.relation.publishversionhttps://www.nature.com/articles/s41598-019-39733-x
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Gorbatenko A] Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York, 10029, USA. [Søkilde R, Newie I, Persson H] BioCare, Strategic Cancer Research Program, Lund, Sweden. Department of Clinical Sciences Lund, Oncology and Pathology, Faculty of Medicine, Lund University, Lund, Sweden. [Sorensen EE] Section for Cell Biology and Physiology, Department of Biology, Faculty of Science, University of Copenhagen, Universitetsparken 13, DK-2100, Copenhagen, Denmark. [Morancho B] Preclinical Research Program, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. CIBERONC. [Arribas J] Preclinical Research Program, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. CIBERONC. Departament de Bioquímica i de Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Spain. Institució Catalana de Recerca i Estudis Avançats, JA, Barcelona, Spain
dc.identifier.pmid30833639
dc.identifier.wos000460123600024
dc.relation.projectidinfo:eu-repo/grantAgreement/ES/PE2013-2016/PI16%2F00253
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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