Relationship between circulating and tissue microRNAs in a murine model of breast cancer.

MiRNAs are key regulators of tumorigenesis that are aberrantly expressed in the circulation and tissue of patients with cancer. The aim of this study was to determine whether miRNA dysregulation in the circulation reflected similar changes in tumour tissue. Athymic nude mice (n = 20) received either...

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Autores principales: Peadar S Waters, Ailbhe M McDermott, Deirdre Wall, Helen M Heneghan, Nicola Miller, John Newell, Michael J Kerin, Roisin M Dwyer
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Publicado: Public Library of Science (PLoS) 2012
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spelling oai:doaj.org-article:952c92e5ad004dd6869b0e7898b487b52021-11-18T08:06:51ZRelationship between circulating and tissue microRNAs in a murine model of breast cancer.1932-620310.1371/journal.pone.0050459https://doaj.org/article/952c92e5ad004dd6869b0e7898b487b52012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23226290/?tool=EBIhttps://doaj.org/toc/1932-6203MiRNAs are key regulators of tumorigenesis that are aberrantly expressed in the circulation and tissue of patients with cancer. The aim of this study was to determine whether miRNA dysregulation in the circulation reflected similar changes in tumour tissue. Athymic nude mice (n = 20) received either a mammary fat pad (n = 8, MFP), or subcutaneous (n = 7, SC) injection of MDA-MB-231 cells. Controls received no tumour cells (n = 5). Tumour volume was monitored weekly and blood sampling performed at weeks 1, 3 and 6 following tumour induction (total n = 60). Animals were sacrificed at week 6 and tumour tissue (n = 15), lungs (n = 20) and enlarged lymph nodes (n = 3) harvested. MicroRNAs were extracted from all samples (n = 98) and relative expression quantified using RQ-PCR. MiR-221 expression was significantly increased in tumour compared to healthy tissue (p<0.001). MiR-10b expression was significantly higher in MFP compared to SC tumours (p<0.05), with the highest levels detected in diseased lymph nodes (p<0.05). MiR-10b was undetectable in the circulation, with no significant change in circulating miR-221 expression detected during disease progression. MiR-195 and miR-497 were significantly decreased in tumour tissue (p<0.05), and also in the circulation of animals 3 weeks following tumour induction (p<0.05). At both tissue and circulating level, a positive correlation was observed between miR-497 and miR-195 (r = 0.61, p<0.001; r = 0.41, p<0.01 respectively). This study highlights the distinct roles of miRNAs in circulation and tissue. It also implicates miRNAs in disease dissemination and progression, which may be important in systemic therapy and biomarker development.Peadar S WatersAilbhe M McDermottDeirdre WallHelen M HeneghanNicola MillerJohn NewellMichael J KerinRoisin M DwyerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 11, p e50459 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Peadar S Waters
Ailbhe M McDermott
Deirdre Wall
Helen M Heneghan
Nicola Miller
John Newell
Michael J Kerin
Roisin M Dwyer
Relationship between circulating and tissue microRNAs in a murine model of breast cancer.
description MiRNAs are key regulators of tumorigenesis that are aberrantly expressed in the circulation and tissue of patients with cancer. The aim of this study was to determine whether miRNA dysregulation in the circulation reflected similar changes in tumour tissue. Athymic nude mice (n = 20) received either a mammary fat pad (n = 8, MFP), or subcutaneous (n = 7, SC) injection of MDA-MB-231 cells. Controls received no tumour cells (n = 5). Tumour volume was monitored weekly and blood sampling performed at weeks 1, 3 and 6 following tumour induction (total n = 60). Animals were sacrificed at week 6 and tumour tissue (n = 15), lungs (n = 20) and enlarged lymph nodes (n = 3) harvested. MicroRNAs were extracted from all samples (n = 98) and relative expression quantified using RQ-PCR. MiR-221 expression was significantly increased in tumour compared to healthy tissue (p<0.001). MiR-10b expression was significantly higher in MFP compared to SC tumours (p<0.05), with the highest levels detected in diseased lymph nodes (p<0.05). MiR-10b was undetectable in the circulation, with no significant change in circulating miR-221 expression detected during disease progression. MiR-195 and miR-497 were significantly decreased in tumour tissue (p<0.05), and also in the circulation of animals 3 weeks following tumour induction (p<0.05). At both tissue and circulating level, a positive correlation was observed between miR-497 and miR-195 (r = 0.61, p<0.001; r = 0.41, p<0.01 respectively). This study highlights the distinct roles of miRNAs in circulation and tissue. It also implicates miRNAs in disease dissemination and progression, which may be important in systemic therapy and biomarker development.
format article
author Peadar S Waters
Ailbhe M McDermott
Deirdre Wall
Helen M Heneghan
Nicola Miller
John Newell
Michael J Kerin
Roisin M Dwyer
author_facet Peadar S Waters
Ailbhe M McDermott
Deirdre Wall
Helen M Heneghan
Nicola Miller
John Newell
Michael J Kerin
Roisin M Dwyer
author_sort Peadar S Waters
title Relationship between circulating and tissue microRNAs in a murine model of breast cancer.
title_short Relationship between circulating and tissue microRNAs in a murine model of breast cancer.
title_full Relationship between circulating and tissue microRNAs in a murine model of breast cancer.
title_fullStr Relationship between circulating and tissue microRNAs in a murine model of breast cancer.
title_full_unstemmed Relationship between circulating and tissue microRNAs in a murine model of breast cancer.
title_sort relationship between circulating and tissue micrornas in a murine model of breast cancer.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/952c92e5ad004dd6869b0e7898b487b5
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