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

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-...

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Autores principales:	Arsalan Amirfallah, Hildur Knutsdottir, Adalgeir Arason, Bylgja Hilmarsdottir, Oskar T. Johannsson, Bjarni A. Agnarsson, Rosa B. Barkardottir, Inga Reynisdottir
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5bdc640f97234803a0e2debaeb2e4ac0
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spelling	oai:doaj.org-article:5bdc640f97234803a0e2debaeb2e4ac02021-11-25T06:19:29ZHsa-miR-21-3p associates with breast cancer patient survival and targets genes in tumor suppressive pathways1932-6203https://doaj.org/article/5bdc640f97234803a0e2debaeb2e4ac02021-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8604322/?tool=EBIhttps://doaj.org/toc/1932-6203Breast 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.Arsalan AmirfallahHildur KnutsdottirAdalgeir ArasonBylgja HilmarsdottirOskar T. JohannssonBjarni A. AgnarssonRosa B. BarkardottirInga ReynisdottirPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Arsalan Amirfallah Hildur Knutsdottir Adalgeir Arason Bylgja Hilmarsdottir Oskar T. Johannsson Bjarni A. Agnarsson Rosa B. Barkardottir Inga Reynisdottir Hsa-miR-21-3p associates with breast cancer patient survival and targets genes in tumor suppressive pathways
description	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.
format	article
author	Arsalan Amirfallah Hildur Knutsdottir Adalgeir Arason Bylgja Hilmarsdottir Oskar T. Johannsson Bjarni A. Agnarsson Rosa B. Barkardottir Inga Reynisdottir
author_facet	Arsalan Amirfallah Hildur Knutsdottir Adalgeir Arason Bylgja Hilmarsdottir Oskar T. Johannsson Bjarni A. Agnarsson Rosa B. Barkardottir Inga Reynisdottir
author_sort	Arsalan Amirfallah
title	Hsa-miR-21-3p associates with breast cancer patient survival and targets genes in tumor suppressive pathways
title_short	Hsa-miR-21-3p associates with breast cancer patient survival and targets genes in tumor suppressive pathways
title_full	Hsa-miR-21-3p associates with breast cancer patient survival and targets genes in tumor suppressive pathways
title_fullStr	Hsa-miR-21-3p associates with breast cancer patient survival and targets genes in tumor suppressive pathways
title_full_unstemmed	Hsa-miR-21-3p associates with breast cancer patient survival and targets genes in tumor suppressive pathways
title_sort	hsa-mir-21-3p associates with breast cancer patient survival and targets genes in tumor suppressive pathways
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/5bdc640f97234803a0e2debaeb2e4ac0
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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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