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dc.contributor.authorBudkova, Zuzana
dc.contributor.authorSigurdardottir, Anna Karen
dc.contributor.authorBriem, Eirikur
dc.contributor.authorBergthorsson, Jon Thor
dc.contributor.authorSigurdsson, Snævar
dc.contributor.authorMagnusson, Magnus Karl
dc.contributor.authorTraustadottir, Gunnhildur Asta
dc.contributor.authorGudjonsson, Thorarinn
dc.contributor.authorHilmarsdottir, Bylgja
dc.date.accessioned2020-08-25T13:53:39Z
dc.date.available2020-08-25T13:53:39Z
dc.date.issued2020-06-16
dc.date.submitted2020-08
dc.identifier.citationBudkova Z, Sigurdardottir AK, Briem E, et al. Expression of ncRNAs on the DLK1-DIO3 Locus Is Associated With Basal and Mesenchymal Phenotype in Breast Epithelial Progenitor Cells. Front Cell Dev Biol. 2020;8:461. Published 2020 Jun 16. doi:10.3389/fcell.2020.00461en_US
dc.identifier.issn2296-634X
dc.identifier.pmid32612992
dc.identifier.doi10.3389/fcell.2020.00461
dc.identifier.urihttp://hdl.handle.net/2336/621487
dc.descriptionTo access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Downloaden_US
dc.description.abstractEpithelial-to-mesenchymal transition (EMT) and its reversed process mesenchymal-to-epithelial transition (MET) play a critical role in epithelial plasticity during development and cancer progression. Among important regulators of these cellular processes are non-coding RNAs (ncRNAs). The imprinted DLK1-DIO3 locus, containing numerous maternally expressed ncRNAs including the lncRNA maternally expressed gene 3 (MEG3) and a cluster of over 50 miRNAs, has been shown to be a modulator of stemness in embryonic stem cells and in cancer progression, potentially through the tumor suppressor role of MEG3. In this study we analyzed the expression pattern and functional role of ncRNAs from the DLK1-DIO3 locus in epithelial plasticity of the breast. We studied their expression in various cell types of breast tissue and revisit the role of the locus in EMT/MET using a breast epithelial progenitor cell line (D492) and its isogenic mesenchymal derivative (D492M). Marked upregulation of ncRNAs from the DLK1-DIO3 locus was seen after EMT induction in two cell line models of EMT. In addition, the expression of MEG3 and the maternally expressed ncRNAs was higher in stromal cells compared to epithelial cell types in primary breast tissue. We also show that expression of MEG3 is concomitant with the expression of the ncRNAs from the DLK1-DIO3 locus and its expression is therefore likely indicative of activation of all ncRNAs at the locus. MEG3 expression is correlated with stromal markers in normal tissue and breast cancer tissue and negatively correlated with the survival of breast cancer patients in two different cohorts. Overexpression of MEG3 using CRISPR activation in a breast epithelial cell line induced partial EMT and enriched for a basal-like phenotype. Conversely, knock down of MEG3 using CRISPR inhibition in a mesenchymal cell line reduced the mesenchymal and basal-like phenotype of the cell line. In summary our study shows that maternally expressed ncRNAs are markers of EMT and suggests that MEG3 is a novel regulator of EMT/MET in breast tissue. Nevertheless, further studies are needed to fully dissect the molecular pathways influenced by non-coding RNAs at the DLK1-DIO3 locus in breast tissue.en_US
dc.description.sponsorshipLandspitali University Hospital Science Fund Icelandic Science and Technology Policy Council Research Fund Icelandic Science and Technology Policy - Grant of Excellence "Visindasjogur Krabbameinsfelagsins" (Icelandic Cancer Society Science Fund) 2017 University of Iceland Research Fund 'Gongum saman', a supporting group for breast cancer research in Icelanden_US
dc.language.isoenen_US
dc.publisherFrontiers Media S.A.en_US
dc.relation.urlhttps://www.frontiersin.org/articles/10.3389/fcell.2020.00461/fullen_US
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308478/en_US
dc.rightsCopyright © 2020 Budkova, Sigurdardottir, Briem, Bergthorsson, Sigurdsson, Magnusson, Traustadottir, Gudjonsson and Hilmarsdottir.
dc.subjectDLK1-DIO3 locusen_US
dc.subjectMEG3en_US
dc.subjectbreast progenitor cellsen_US
dc.subjectepithelial plasticityen_US
dc.subjectncRNAsen_US
dc.titleExpression of ncRNAs on the DLK1-DIO3 Locus Is Associated With Basal and Mesenchymal Phenotype in Breast Epithelial Progenitor Cells.en_US
dc.typeArticleen_US
dc.contributor.department1Stem Cell Research Unit, Biomedical Center, Department of Anatomy, Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland. 2Department of Laboratory Hematology, Landspitali - University Hospital, Reykjavik, Iceland. 3Department of Pharmacology and Toxicology, Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland. 4Department of Pathology, Landspitali - University Hospital, Reykjavik, Iceland.en_US
dc.identifier.journalFrontiers in cell and developmental biologyen_US
dc.rights.accessOpen Access - Opinn aðganguren_US
dc.departmentcodeNAF12
dc.source.journaltitleFrontiers in cell and developmental biology
dc.source.volume8
dc.source.beginpage461
dc.source.endpage
refterms.dateFOA2020-08-25T13:53:39Z
dc.source.countrySwitzerland


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