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Hsa-miR-21-3p associates with breast cancer patient survival and targets genes in tumor suppressive pathways

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dc.contributor University of Iceland
dc.contributor.author Amirfallah, Arsalan
dc.contributor.author Knutsdottir, Hildur
dc.contributor.author Arason, Aðalgeir
dc.contributor.author Hilmarsdóttir, Bylgja
dc.contributor.author Jóhannsson, Óskar Þór
dc.contributor.author Agnarsson, Bjarni Agnar
dc.contributor.author Barkardottir, Rosa B.
dc.contributor.author Reynisdottir, Inga
dc.date.accessioned 2021-12-18T01:02:36Z
dc.date.available 2021-12-18T01:02:36Z
dc.date.issued 2021-11-19
dc.identifier.citation Amirfallah , A , Knutsdottir , H , Arason , A , Hilmarsdóttir , B , Jóhannsson , Ó Þ , Agnarsson , B A , Barkardottir , R B & Reynisdottir , I 2021 , ' Hsa-miR-21-3p associates with breast cancer patient survival and targets genes in tumor suppressive pathways ' , PLoS ONE , vol. 16 , no. 11 , e0260327 , pp. e0260327 . https://doi.org/10.1371/journal.pone.0260327
dc.identifier.issn 1932-6203
dc.identifier.other PURE: 43427994
dc.identifier.other PURE UUID: 67a68415-a5a3-4016-befa-b6346e318854
dc.identifier.other Scopus: 85119996535
dc.identifier.other unpaywall: 10.1371/journal.pone.0260327
dc.identifier.uri https://hdl.handle.net/20.500.11815/2763
dc.description Publisher Copyright: Copyright: © 2021 Amirfallah et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.description.abstract Breast cancer is the cancer most often diagnosed in women. MicroRNAs (MIRs) are short RNA molecules that bind mRNA resulting in their downregulation. MIR21 has been shown to be an oncomiR in most cancer types, including breast cancer. Most of the effects of miR-21 have been attributed to hsa-miR-21-5p that is transcribed from the leading strand of MIR21, but hsa-miR-21-3p (miR-21-3p), transcribed from the lagging strand, is much less studied. The aim of the study is to analyze whether expression of miR-21-3p is prognostic for breast cancer. MiR-21-3p association with survival, clinical and pathological characteristics was analyzed in a large breast cancer cohort and validated in three separate cohorts, including TCGA and METABRIC. Analytical tools were also used to infer miR-21-3p function and to identify potential target genes and functional pathways. The results showed that in the exploration cohort, high miR-21-3p levels associated with shorter survival and lymph node positivity. In the three validation cohorts, high miR-21-3p levels associated with pathological characteristics that predict worse prognosis. Specifically, in the largest validation cohort, METABRIC (n = 1174), high miR-21-3p levels associated with large tumors, a high grade, lymph node and HER2 positivity, and shorter breast-cancer-specific survival (HR = 1.38, CI 1.13–1.68). This association remained significant after adjusting for confounding factors. The genes with expression levels that correlated with miR-21-3p were enriched in particular pathways, including the epithelial-to-mesenchymal transition and proliferation. Among the most significantly downregulated targets were MAT2A and the tumor suppressive genes STARD13 and ZNF132. The results from this study emphasize that both 3p- and 5p-arms from a MIR warrant independent study. The data show that miR-21-3p overexpression in breast tumors is a marker of worse breast cancer progression and it affects genes in pathways that drive breast cancer by down-regulating tumor suppressor genes. The results suggest miR-21-3p as a potential biomarker.
dc.format.extent 18
dc.format.extent e0260327
dc.language.iso en
dc.relation.ispartofseries PLoS ONE; 16(11)
dc.rights info:eu-repo/semantics/openAccess
dc.subject Brjóstakrabbamein
dc.subject Gen
dc.subject Náttúrufræðingar
dc.subject Krabbameinslæknisfræði
dc.subject Meinafræði
dc.subject Breast cancer
dc.subject Breast tumors
dc.subject Malignant tumors
dc.subject Tumor suppressor genes
dc.subject Prostate cancer
dc.subject Metaanalysis
dc.subject Breast tissue
dc.subject Clinical pathology
dc.subject Multidisciplinary
dc.title Hsa-miR-21-3p associates with breast cancer patient survival and targets genes in tumor suppressive pathways
dc.type /dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article
dc.description.version Peer reviewed
dc.identifier.pmid 34797887
dc.identifier.doi https://doi.org/10.1371/journal.pone.0260327
dc.relation.url http://www.scopus.com/inward/record.url?scp=85119996535&partnerID=8YFLogxK
dc.contributor.department Clinical Laboratory Services, Diagnostics and Blood Bank
dc.contributor.department Cancer Center
dc.contributor.department Faculty of Medicine

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