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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Veröffentlicht in:PloS one 2012-11, Vol.7 (11), p.e50459-e50459
Hauptverfasser: Waters, Peadar S, McDermott, Ailbhe M, Wall, Deirdre, Heneghan, Helen M, Miller, Nicola, Newell, John, Kerin, Michael J, Dwyer, Roisin M
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container_end_page e50459
container_issue 11
container_start_page e50459
container_title PloS one
container_volume 7
creator Waters, Peadar S
McDermott, Ailbhe M
Wall, Deirdre
Heneghan, Helen M
Miller, Nicola
Newell, John
Kerin, Michael J
Dwyer, Roisin M
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
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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.]]></description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0050459</identifier><identifier>PMID: 23226290</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aberration ; Animal models ; Animals ; Applied mathematics ; Bioindicators ; Biology ; Biomarkers ; Biomarkers, Tumor - blood ; Biomarkers, Tumor - genetics ; Blood tests ; Breast cancer ; Breast Neoplasms - blood ; Breast Neoplasms - diagnosis ; Breast Neoplasms - genetics ; Breast Neoplasms - pathology ; Cancer ; Cancer research ; Cell cycle ; Cell Line, Tumor ; Circulation ; Colorectal cancer ; Discipline ; Disease ; Disease Models, Animal ; Disease Progression ; Female ; Fluorides ; Gastric cancer ; Gene expression ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Injections, Subcutaneous ; Lung - metabolism ; Lung - pathology ; Lungs ; Lymph nodes ; Lymph Nodes - metabolism ; Lymph Nodes - pathology ; Mammography ; Medical prognosis ; Medicine ; Metastasis ; Mice ; Mice, Nude ; MicroRNA ; MicroRNAs ; MicroRNAs - blood ; MicroRNAs - genetics ; miRNA ; Neoplasm Transplantation ; Prostate cancer ; Proteins ; Regulators ; Stomach cancer ; Studies ; Surgery ; Tissues ; Tumor Burden ; Tumorigenesis ; Tumors</subject><ispartof>PloS one, 2012-11, Vol.7 (11), p.e50459-e50459</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Waters et al. 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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). 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It also implicates miRNAs in disease dissemination and progression, which may be important in systemic therapy and biomarker development.]]></description><subject>Aberration</subject><subject>Animal models</subject><subject>Animals</subject><subject>Applied mathematics</subject><subject>Bioindicators</subject><subject>Biology</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - blood</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Blood tests</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - blood</subject><subject>Breast Neoplasms - diagnosis</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - pathology</subject><subject>Cancer</subject><subject>Cancer research</subject><subject>Cell cycle</subject><subject>Cell Line, Tumor</subject><subject>Circulation</subject><subject>Colorectal cancer</subject><subject>Discipline</subject><subject>Disease</subject><subject>Disease Models, Animal</subject><subject>Disease Progression</subject><subject>Female</subject><subject>Fluorides</subject><subject>Gastric cancer</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Injections, Subcutaneous</subject><subject>Lung - 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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.]]></abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23226290</pmid><doi>10.1371/journal.pone.0050459</doi><tpages>e50459</tpages><oa>free_for_read</oa></addata></record>
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subjects Aberration
Animal models
Animals
Applied mathematics
Bioindicators
Biology
Biomarkers
Biomarkers, Tumor - blood
Biomarkers, Tumor - genetics
Blood tests
Breast cancer
Breast Neoplasms - blood
Breast Neoplasms - diagnosis
Breast Neoplasms - genetics
Breast Neoplasms - pathology
Cancer
Cancer research
Cell cycle
Cell Line, Tumor
Circulation
Colorectal cancer
Discipline
Disease
Disease Models, Animal
Disease Progression
Female
Fluorides
Gastric cancer
Gene expression
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Injections, Subcutaneous
Lung - metabolism
Lung - pathology
Lungs
Lymph nodes
Lymph Nodes - metabolism
Lymph Nodes - pathology
Mammography
Medical prognosis
Medicine
Metastasis
Mice
Mice, Nude
MicroRNA
MicroRNAs
MicroRNAs - blood
MicroRNAs - genetics
miRNA
Neoplasm Transplantation
Prostate cancer
Proteins
Regulators
Stomach cancer
Studies
Surgery
Tissues
Tumor Burden
Tumorigenesis
Tumors
title Relationship between circulating and tissue microRNAs in a murine model of breast cancer
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