Obesity impacts the regulation of miR-10b and its targets in primary breast tumors
dc.contributor.author | Meerson, A | |
dc.contributor.author | Eliraz, Y | |
dc.contributor.author | Yehuda, H | |
dc.contributor.author | Knight, B | |
dc.contributor.author | Crundwell, M | |
dc.contributor.author | Ferguson, D | |
dc.contributor.author | Lee, BP | |
dc.contributor.author | Harries, LW | |
dc.date.accessioned | 2019-05-22T13:14:13Z | |
dc.date.issued | 2019-01-18 | |
dc.description.abstract | Background: Obesity increases breast cancer (BC) risk in post-menopausal women by mostly unknown molecular mechanisms which may partly be regulated by microRNAs (miRNAs). Methods: We isolated RNA from paired benign and malignant biopsies from 83 BC patients and determined miRNA profiles in samples from 12 women at the extremes of the BMI distribution by RNA-seq. Candidates were validated in all samples. Associations between miR-10b expression and validated target transcript levels, and effects of targeted manipulation of miR-10b levels in a primary BC cell line on proliferation and invasion potential, were explored. Results: Of the 148 miRNAs robustly expressed in breast tissues, the levels of miR-21, miR-10b, miR-451a, miR-30c, and miR-378d were significantly associated with presence of cancer. Of these, miR-10b showed a stronger down-regulation in the tumors of the obese subjects, as opposed to the lean. In ductal but not lobular tumors, significant inverse correlations were observed between the tumor levels of miR-10b and miR-30c and the mRNA levels of cancer-relevant target genes SRSF1, PIEZO1, MAPRE1, CDKN2A, TP-53 and TRA2B, as well as tumor grade. Suppression of miR-10b levels in BT-549 primary BC-derived cells increased cell proliferation and invasive capacity, while exogenous miR-10b mimic decreased invasion. Manipulation of miR-10b levels also inversely affected the mRNA levels of miR-10b targets BCL2L11, PIEZO1 and NCOR2. Conclusions: Our findings suggest that miR-10b may be a mediator between obesity and cancer in post-menopausal women, regulating several known cancer-relevant genes. MiR-10b expression may have diagnostic and therapeutic implications for the incidence and prognosis of BC in obese women. | en_GB |
dc.description.sponsorship | European Union’s FP7-REGPOT-2012-2013-1 | en_GB |
dc.description.sponsorship | Israel Cancer Research Fund (ICRF) Gesher Award | en_GB |
dc.description.sponsorship | D-Cure/MOH-CSO Diabetes Research Grant | en_GB |
dc.description.sponsorship | Academy of Medical Sciences Daniel Turnberg Travel Award | en_GB |
dc.description.sponsorship | National Institute for Health Research (NIHR) Exeter Clinical Research Facility | en_GB |
dc.identifier.citation | Vol. 19 (86) | en_GB |
dc.identifier.doi | 10.1186/s12885-019-5300-6 | |
dc.identifier.grantnumber | 316157 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/37181 | |
dc.language.iso | en | en_GB |
dc.publisher | BMC | en_GB |
dc.rights | © 2019 The Author(s). This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. | en_GB |
dc.subject | miR-10b | en_GB |
dc.subject | Breast cancer | en_GB |
dc.subject | Obesity | en_GB |
dc.subject | microRNA | en_GB |
dc.subject | Tumor suppressors | en_GB |
dc.subject | Oncogenes | en_GB |
dc.title | Obesity impacts the regulation of miR-10b and its targets in primary breast tumors | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2019-05-22T13:14:13Z | |
dc.description | This is the final version. Available from BMC via the DOI in this record. | en_GB |
dc.description | RNA-seq datasets generated during the current study are available in the SRA repository (BioProject ID PRJNA494326). Other datasets supporting the conclusions of this article are included within the article and its Additional files. | en_GB |
dc.identifier.journal | BMC Cancer | en_GB |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2019-01-10 | |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2019-01-10 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2019-05-22T13:07:33Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2019-05-22T13:14:19Z | |
refterms.panel | A | en_GB |
refterms.depositException | publishedGoldOA |
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Except where otherwise noted, this item's licence is described as © 2019 The Author(s). This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.