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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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. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2012 Waters et al 2012 Waters et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-6992365db44e91c8a59f75049a317a3d825688cf699539a05bb1737a8103c44d3</citedby><cites>FETCH-LOGICAL-c692t-6992365db44e91c8a59f75049a317a3d825688cf699539a05bb1737a8103c44d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3511577/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3511577/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79472,79473</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23226290$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Cheng, Jin Q.</contributor><creatorcontrib>Waters, Peadar S</creatorcontrib><creatorcontrib>McDermott, Ailbhe M</creatorcontrib><creatorcontrib>Wall, Deirdre</creatorcontrib><creatorcontrib>Heneghan, Helen M</creatorcontrib><creatorcontrib>Miller, Nicola</creatorcontrib><creatorcontrib>Newell, John</creatorcontrib><creatorcontrib>Kerin, Michael J</creatorcontrib><creatorcontrib>Dwyer, Roisin M</creatorcontrib><title>Relationship between circulating and tissue microRNAs in a murine model of breast cancer</title><title>PloS one</title><addtitle>PLoS One</addtitle><description><![CDATA[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.]]></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 - metabolism</subject><subject>Lung - pathology</subject><subject>Lungs</subject><subject>Lymph nodes</subject><subject>Lymph Nodes - metabolism</subject><subject>Lymph Nodes - pathology</subject><subject>Mammography</subject><subject>Medical prognosis</subject><subject>Medicine</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>MicroRNA</subject><subject>MicroRNAs</subject><subject>MicroRNAs - blood</subject><subject>MicroRNAs - genetics</subject><subject>miRNA</subject><subject>Neoplasm Transplantation</subject><subject>Prostate cancer</subject><subject>Proteins</subject><subject>Regulators</subject><subject>Stomach cancer</subject><subject>Studies</subject><subject>Surgery</subject><subject>Tissues</subject><subject>Tumor Burden</subject><subject>Tumorigenesis</subject><subject>Tumors</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk0uP0zAQxyMEYpeFb4AgEhKCQ4sfsR1fkKoVj0orVioPcbMcZ9K6Su1iJzy-PU6bXTVoD8gHW-Pf_D0znsmypxjNMRX4zdb3wel2vvcO5ggxVDB5LzvHkpIZJ4jePzmfZY9i3CaIlpw_zM4IJYQTic6z7ytodWe9ixu7zyvofgG43Nhg-sHu1rl2dd7ZGHvId9YEv_q0iLl1uc53fbAuWX0Nbe6bvAqgY5cb7QyEx9mDRrcRnoz7Rfb1_bsvlx9nV9cflpeLq5nhknQzLiWhnNVVUYDEptRMNiLlIjXFQtO6JIyXpWkSx6jUiFUVFlToEiNqiqKmF9nzo-6-9VGNRYkKU4YRF4QWiVgeidrrrdoHu9Phj_LaqoPBh7XSobOmBSUZMZIA0zVCRV3zkssKgShlWRWlqFjSeju-1lc7qA24Luh2Ijq9cXaj1v6nSuFgJkQSeDUKBP-jh9ipnY0G2lY78H2Km9CUPpUH9MU_6N3ZjdRapwSsa3x61wyialGIVDbK5RD3_A4qrRrSp6YOamyyTxxeTxwS08Hvbq37GNXy8-r_2etvU_blCbsB3Xab6Nv-0IJTsDiCqeViDNDcFhkjNQzATTXUMABqHIDk9uz0g26dbjqe_gUFUf59</recordid><startdate>20121130</startdate><enddate>20121130</enddate><creator>Waters, Peadar S</creator><creator>McDermott, Ailbhe M</creator><creator>Wall, Deirdre</creator><creator>Heneghan, Helen M</creator><creator>Miller, Nicola</creator><creator>Newell, John</creator><creator>Kerin, Michael J</creator><creator>Dwyer, Roisin M</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20121130</creationdate><title>Relationship between circulating and tissue microRNAs in a murine model of breast cancer</title><author>Waters, Peadar S ; McDermott, Ailbhe M ; Wall, Deirdre ; Heneghan, Helen M ; Miller, Nicola ; Newell, John ; Kerin, Michael J ; Dwyer, Roisin M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-6992365db44e91c8a59f75049a317a3d825688cf699539a05bb1737a8103c44d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Aberration</topic><topic>Animal models</topic><topic>Animals</topic><topic>Applied mathematics</topic><topic>Bioindicators</topic><topic>Biology</topic><topic>Biomarkers</topic><topic>Biomarkers, Tumor - blood</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Blood tests</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - blood</topic><topic>Breast Neoplasms - diagnosis</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - pathology</topic><topic>Cancer</topic><topic>Cancer research</topic><topic>Cell cycle</topic><topic>Cell Line, Tumor</topic><topic>Circulation</topic><topic>Colorectal cancer</topic><topic>Discipline</topic><topic>Disease</topic><topic>Disease Models, Animal</topic><topic>Disease Progression</topic><topic>Female</topic><topic>Fluorides</topic><topic>Gastric cancer</topic><topic>Gene expression</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humans</topic><topic>Injections, Subcutaneous</topic><topic>Lung - metabolism</topic><topic>Lung - pathology</topic><topic>Lungs</topic><topic>Lymph nodes</topic><topic>Lymph Nodes - metabolism</topic><topic>Lymph Nodes - pathology</topic><topic>Mammography</topic><topic>Medical prognosis</topic><topic>Medicine</topic><topic>Metastasis</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>MicroRNA</topic><topic>MicroRNAs</topic><topic>MicroRNAs - 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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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