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CpG promoter hypo-methylation and up-regulation of microRNA-190b in hormone receptor-positive breast cancer

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dc.contributor Háskóli Íslands
dc.contributor University of Iceland
dc.contributor.author Frick, Elisabet
dc.contributor.author Gudjonsson, Thorkell
dc.contributor.author Eyfjörð, Jórunn Erla
dc.contributor.author Jonasson, Jon
dc.contributor.author Tryggvadóttir, Laufey
dc.contributor.author Stefansson, Olafur
dc.contributor.author Sigurdsson, Stefan
dc.date.accessioned 2020-08-24T10:58:33Z
dc.date.available 2020-08-24T10:58:33Z
dc.date.issued 2019-07-23
dc.identifier.citation Frick E., Gudjonsson T., Eyfjord J., Jonasson J., Tryggvadóttir L., Stefansson O., Sigurdsson S. CpG promoter hypo-methylation and up-regulation of microRNA-190b in hormone receptor-positive breast cancer. Oncotarget. 2019; 10: 4664-4678. Retrieved from https://www.oncotarget.com/article/27083/text/
dc.identifier.issn 1949-2553
dc.identifier.uri https://hdl.handle.net/20.500.11815/2002
dc.description Publisher's version (útgefin grein)
dc.description.abstract Estrogen receptor-positive breast cancer is subdivided into subtypes LuminalA and LuminalB, based on different expression patterns. MicroRNA-190b has been reported to be up-regulated in estrogen receptor-positive breast cancers. In this study we aimed to investigate the role of CpG promoter methylation in regulating miR-190b expression and its impact on clinical presentation and prognosis. DNA methylation analysis for the promotor of microRNA-190b was performed by pyrosequencing 549 primary breast tumors, of which 62 were carriers of the BRCA2999del5 founder mutation, 71 proximal normal breast samples and 16 breast derived cell lines. MicroRNA-190b expression was analysed in 67 primary breast tumors, 14 paired normal breast samples and 16 breast derived cell lines. Tissue microarrays (TMAs) were available for ER (n = 436), PR (n = 436), HER-2 (N = 258) and Ki67 (n = 248). MiR-190b had reduced promoter methylation in estrogen receptor-positive breast cancers (P = 1.02e–12, Median values: ER+ 24.3, ER– 38.26) and miR-190b’s expression was up-regulated in a correlative manner (P = 1.83e–06, Spearman’s rho –0.62). Through breast cancer specific survival analysis, we demonstrated that LuminalA patients exhibiting miR-190b hypo-methylation had better survival than other patients (P = 0.034, HR = 0.29, 95% CI 0.09-0.91). We, furthermore, demonstrated that miR-190b hypo-methylation occurs less frequently in ER+ tumors from BRCA2999del5 mutation carriers than in non-mutated individuals (P = 0.038, Χ2 = 4.32, n = 335). Our results suggest that upregulation of miR-190b may occur through loss of promoter DNA methylation during the development of estrogen-receptor (ER) positive breast cancers, and that miR-190b hypo-methylation leads to increased breast cancer specific survival within the LuminalA- subtype but not LuminalB.
dc.description.sponsorship This work was funded b y Gongum Saman (EAF), The Icelandic cancer society (TG), and Icelandic Centre for Research RANNIS grant ID # 141395
dc.format.extent 4664-4678
dc.language.iso en
dc.publisher Impact Journals, LLC
dc.relation.ispartofseries Oncotarget;10(45)
dc.rights info:eu-repo/semantics/openAccess
dc.subject Oncology
dc.subject DNA methylation
dc.subject Prognosis
dc.subject Breast cancer
dc.subject Estrogen receptor
dc.subject Brjóstakrabbamein
dc.subject DNA-rannsóknir
dc.subject Estrógen
dc.subject Batahorfur
dc.title CpG promoter hypo-methylation and up-regulation of microRNA-190b in hormone receptor-positive breast cancer
dc.type info:eu-repo/semantics/article
dcterms.license Copyright: Frick et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
dc.description.version Peer reviewed
dc.identifier.journal Oncotarget
dc.identifier.doi 10.18632/oncotarget.27083
dc.relation.url https://www.oncotarget.com/lookup/doi/10.18632/oncotarget.27083
dc.contributor.department Læknadeild (HÍ)
dc.contributor.department Faculty of Medicine (UI)
dc.contributor.school Heilbrigðisvísindasvið (HÍ)
dc.contributor.school School of Health Sciences (UI)


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