miR-221/222 targets adiponectin receptor 1 to promote the epithelial-to-mesenchymal transition in breast cancer
The epithelial-to-mesenchymal transition (EMT) is a highly conserved physiological program involved in development and tissue repair; however, its aberrant activation has been implicated in accelerating the progression of a variety of cancers. In breast cancer, the microRNAs (miRNAs) miR-221 and miR...
Gespeichert in:
| Veröffentlicht in: | PloS one 2013-06, Vol.8 (6), p.e66502-e66502 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e66502 |
|---|---|
| container_issue | 6 |
| container_start_page | e66502 |
| container_title | PloS one |
| container_volume | 8 |
| creator | Hwang, Michael S Yu, Nancy Stinson, Susanna Y Yue, Peng Newman, Robert J Allan, Bernard B Dornan, David |
| description | The epithelial-to-mesenchymal transition (EMT) is a highly conserved physiological program involved in development and tissue repair; however, its aberrant activation has been implicated in accelerating the progression of a variety of cancers. In breast cancer, the microRNAs (miRNAs) miR-221 and miR-222 (miR-221/222) are differentially expressed in the clinically more aggressive basal-like subtype compared to luminal subtype of breast cancer and upregulation of miR-221/222 induces the EMT by targeting the 3' untranslated region (3'UTR) of the GATA family transcriptional repressor TRPS1 (tricho-rhino-phalangeal syndrome type 1). The complete mechanism through which miR-221/222 promotes the EMT, however, is not fully understood. We identified adiponectin receptor 1 (ADIPOR1), a receptor for the adipocytokine adiponectin, as a direct target of miR-221/222. ADIPOR1 is expressed at higher levels in the luminal compared to the basal-like subtype of breast cancer cell lines, which can be reduced by miR-221/222 targeting of its 3'UTR. In addition, miR-221/222 were negatively correlated with ADIPOR1 expression across breast cancer cell lines and tumors. ADIPOR1 depletion by siRNA in MCF10A cells induced the EMT and increased cell invasion. Depletion of ADIPOR1 by siRNA induced activation of the canonical nuclear factor-kappaB (NF-κB) and subsequent phosphorylation of signal transducer and activator of transcription 3 (STAT3) in an interleukin 6 (IL6)-dependent manner. Finally, overexpression of ADIPOR1 in the basal-like cell line, MDA-MB-231, attenuated cell invasion and promoted the mesenchymal-to-epithelial transition (MET). We conclude that ADIPOR1 negatively regulates EMT in breast cancer and provides an additional node by which miR-221/222 induces the EMT. These results suggest that ADIPOR1 may play an important role in breast cancer progression and metastasis, and could potentially offer an alternative therapeutic strategy for basal-like breast cancer patients. |
| doi_str_mv | 10.1371/journal.pone.0066502 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1366648246</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A478325805</galeid><doaj_id>oai_doaj_org_article_630e56cb583c4337b432db448afc9f31</doaj_id><sourcerecordid>A478325805</sourcerecordid><originalsourceid>FETCH-LOGICAL-c758t-bb0a61245795b9288dfe168c8669f4c78df26946b6f135f6dd3fe016e7331dd83</originalsourceid><addsrcrecordid>eNqNk0tr3DAQx01padJtv0FpDYXSHrzRy7J8KYTQx0IgkD6uQpbHu1pkayPJpfn21WadsC45FB0kjX7z12g0k2WvMVpiWuGzrRv9oOxy5wZYIsR5iciT7BTXlBScIPr0aH2SvQhhi1BJBefPsxNCq4rzqj7NXG-uC0LwGSEkj8qvIYZctWavqqMZcg8adtH5HOfR5TvvehchjxvIYWfSZI2yRXRFDwEGvbntlc2jV0Mw0bghTwqNBxVirtWgwb_MnnXKBng1zYvs55fPPy6-FZdXX1cX55eFrkoRi6ZBimPCyqoum5oI0XaAudAp_Lpjukp7wmvGG95hWna8bWkHCHOoKMVtK-gie3vQ3VkX5JSrIDHlnDNBGE_E6kC0Tm3lzpte-VvplJF3BufXUvlotAXJKYKS66YUVDNKq4ZR0jaMCdXpuqM4aX2abhubHloNQ0qBnYnOTwazkWv3W9L0CYiRJPBhEvDuZoQQZW-CBmvVAG68i7uusBA1Sui7f9DHXzdRa5UeYIbOpXv1XlSes0pQUopUDYts-QiVRgu90akEOpPsM4ePM4fERPgT12oMQa6-X_8_e_Vrzr4_YjegbNwEZ8d9DYU5yA6g9i4ED91DkjGS-764z4bcV7Cc-iK5vTn-oAen-0agfwEYxAde</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1366648246</pqid></control><display><type>article</type><title>miR-221/222 targets adiponectin receptor 1 to promote the epithelial-to-mesenchymal transition in breast cancer</title><source>Public Library of Science (PLoS) Journals Open Access</source><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Hwang, Michael S ; Yu, Nancy ; Stinson, Susanna Y ; Yue, Peng ; Newman, Robert J ; Allan, Bernard B ; Dornan, David</creator><contributor>Katz, Elad</contributor><creatorcontrib>Hwang, Michael S ; Yu, Nancy ; Stinson, Susanna Y ; Yue, Peng ; Newman, Robert J ; Allan, Bernard B ; Dornan, David ; Katz, Elad</creatorcontrib><description>The epithelial-to-mesenchymal transition (EMT) is a highly conserved physiological program involved in development and tissue repair; however, its aberrant activation has been implicated in accelerating the progression of a variety of cancers. In breast cancer, the microRNAs (miRNAs) miR-221 and miR-222 (miR-221/222) are differentially expressed in the clinically more aggressive basal-like subtype compared to luminal subtype of breast cancer and upregulation of miR-221/222 induces the EMT by targeting the 3' untranslated region (3'UTR) of the GATA family transcriptional repressor TRPS1 (tricho-rhino-phalangeal syndrome type 1). The complete mechanism through which miR-221/222 promotes the EMT, however, is not fully understood. We identified adiponectin receptor 1 (ADIPOR1), a receptor for the adipocytokine adiponectin, as a direct target of miR-221/222. ADIPOR1 is expressed at higher levels in the luminal compared to the basal-like subtype of breast cancer cell lines, which can be reduced by miR-221/222 targeting of its 3'UTR. In addition, miR-221/222 were negatively correlated with ADIPOR1 expression across breast cancer cell lines and tumors. ADIPOR1 depletion by siRNA in MCF10A cells induced the EMT and increased cell invasion. Depletion of ADIPOR1 by siRNA induced activation of the canonical nuclear factor-kappaB (NF-κB) and subsequent phosphorylation of signal transducer and activator of transcription 3 (STAT3) in an interleukin 6 (IL6)-dependent manner. Finally, overexpression of ADIPOR1 in the basal-like cell line, MDA-MB-231, attenuated cell invasion and promoted the mesenchymal-to-epithelial transition (MET). We conclude that ADIPOR1 negatively regulates EMT in breast cancer and provides an additional node by which miR-221/222 induces the EMT. These results suggest that ADIPOR1 may play an important role in breast cancer progression and metastasis, and could potentially offer an alternative therapeutic strategy for basal-like breast cancer patients.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0066502</identifier><identifier>PMID: 23776679</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>3' Untranslated regions ; Aberration ; Activation ; Adiponectin ; Apoptosis ; Biology ; Biotechnology ; Blotting, Western ; Breast cancer ; Breast Neoplasms - genetics ; Breast Neoplasms - metabolism ; Cancer ; Cell Line, Tumor ; Comparative analysis ; Depletion ; Development and progression ; Epithelial-Mesenchymal Transition - genetics ; Epithelial-Mesenchymal Transition - physiology ; Female ; Fluorescent Antibody Technique ; Gene expression ; Gene Expression Regulation, Neoplastic - genetics ; Gene Expression Regulation, Neoplastic - physiology ; Humans ; Insulin resistance ; Interleukin 6 ; Kinases ; Medicine ; Mesenchyme ; Metastases ; Metastasis ; MicroRNA ; MicroRNAs ; MicroRNAs - genetics ; MicroRNAs - metabolism ; miRNA ; Molecular biology ; NF-κB protein ; Pathogenesis ; Phosphorylation ; Physiological aspects ; Real-Time Polymerase Chain Reaction ; Receptors, Adiponectin - genetics ; Receptors, Adiponectin - metabolism ; Rodents ; siRNA ; Stat3 protein ; Stem cells ; Transcription ; Transcription factors ; Tricho-rhino-phalangeal syndrome ; Tumor cell lines ; Tumors</subject><ispartof>PloS one, 2013-06, Vol.8 (6), p.e66502-e66502</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Hwang 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>2013 Hwang et al 2013 Hwang et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-bb0a61245795b9288dfe168c8669f4c78df26946b6f135f6dd3fe016e7331dd83</citedby><cites>FETCH-LOGICAL-c758t-bb0a61245795b9288dfe168c8669f4c78df26946b6f135f6dd3fe016e7331dd83</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/PMC3679042/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3679042/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23776679$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Katz, Elad</contributor><creatorcontrib>Hwang, Michael S</creatorcontrib><creatorcontrib>Yu, Nancy</creatorcontrib><creatorcontrib>Stinson, Susanna Y</creatorcontrib><creatorcontrib>Yue, Peng</creatorcontrib><creatorcontrib>Newman, Robert J</creatorcontrib><creatorcontrib>Allan, Bernard B</creatorcontrib><creatorcontrib>Dornan, David</creatorcontrib><title>miR-221/222 targets adiponectin receptor 1 to promote the epithelial-to-mesenchymal transition in breast cancer</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The epithelial-to-mesenchymal transition (EMT) is a highly conserved physiological program involved in development and tissue repair; however, its aberrant activation has been implicated in accelerating the progression of a variety of cancers. In breast cancer, the microRNAs (miRNAs) miR-221 and miR-222 (miR-221/222) are differentially expressed in the clinically more aggressive basal-like subtype compared to luminal subtype of breast cancer and upregulation of miR-221/222 induces the EMT by targeting the 3' untranslated region (3'UTR) of the GATA family transcriptional repressor TRPS1 (tricho-rhino-phalangeal syndrome type 1). The complete mechanism through which miR-221/222 promotes the EMT, however, is not fully understood. We identified adiponectin receptor 1 (ADIPOR1), a receptor for the adipocytokine adiponectin, as a direct target of miR-221/222. ADIPOR1 is expressed at higher levels in the luminal compared to the basal-like subtype of breast cancer cell lines, which can be reduced by miR-221/222 targeting of its 3'UTR. In addition, miR-221/222 were negatively correlated with ADIPOR1 expression across breast cancer cell lines and tumors. ADIPOR1 depletion by siRNA in MCF10A cells induced the EMT and increased cell invasion. Depletion of ADIPOR1 by siRNA induced activation of the canonical nuclear factor-kappaB (NF-κB) and subsequent phosphorylation of signal transducer and activator of transcription 3 (STAT3) in an interleukin 6 (IL6)-dependent manner. Finally, overexpression of ADIPOR1 in the basal-like cell line, MDA-MB-231, attenuated cell invasion and promoted the mesenchymal-to-epithelial transition (MET). We conclude that ADIPOR1 negatively regulates EMT in breast cancer and provides an additional node by which miR-221/222 induces the EMT. These results suggest that ADIPOR1 may play an important role in breast cancer progression and metastasis, and could potentially offer an alternative therapeutic strategy for basal-like breast cancer patients.</description><subject>3' Untranslated regions</subject><subject>Aberration</subject><subject>Activation</subject><subject>Adiponectin</subject><subject>Apoptosis</subject><subject>Biology</subject><subject>Biotechnology</subject><subject>Blotting, Western</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - metabolism</subject><subject>Cancer</subject><subject>Cell Line, Tumor</subject><subject>Comparative analysis</subject><subject>Depletion</subject><subject>Development and progression</subject><subject>Epithelial-Mesenchymal Transition - genetics</subject><subject>Epithelial-Mesenchymal Transition - physiology</subject><subject>Female</subject><subject>Fluorescent Antibody Technique</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic - genetics</subject><subject>Gene Expression Regulation, Neoplastic - physiology</subject><subject>Humans</subject><subject>Insulin resistance</subject><subject>Interleukin 6</subject><subject>Kinases</subject><subject>Medicine</subject><subject>Mesenchyme</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>MicroRNA</subject><subject>MicroRNAs</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>miRNA</subject><subject>Molecular biology</subject><subject>NF-κB protein</subject><subject>Pathogenesis</subject><subject>Phosphorylation</subject><subject>Physiological aspects</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Receptors, Adiponectin - genetics</subject><subject>Receptors, Adiponectin - metabolism</subject><subject>Rodents</subject><subject>siRNA</subject><subject>Stat3 protein</subject><subject>Stem cells</subject><subject>Transcription</subject><subject>Transcription factors</subject><subject>Tricho-rhino-phalangeal syndrome</subject><subject>Tumor cell lines</subject><subject>Tumors</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk0tr3DAQx01padJtv0FpDYXSHrzRy7J8KYTQx0IgkD6uQpbHu1pkayPJpfn21WadsC45FB0kjX7z12g0k2WvMVpiWuGzrRv9oOxy5wZYIsR5iciT7BTXlBScIPr0aH2SvQhhi1BJBefPsxNCq4rzqj7NXG-uC0LwGSEkj8qvIYZctWavqqMZcg8adtH5HOfR5TvvehchjxvIYWfSZI2yRXRFDwEGvbntlc2jV0Mw0bghTwqNBxVirtWgwb_MnnXKBng1zYvs55fPPy6-FZdXX1cX55eFrkoRi6ZBimPCyqoum5oI0XaAudAp_Lpjukp7wmvGG95hWna8bWkHCHOoKMVtK-gie3vQ3VkX5JSrIDHlnDNBGE_E6kC0Tm3lzpte-VvplJF3BufXUvlotAXJKYKS66YUVDNKq4ZR0jaMCdXpuqM4aX2abhubHloNQ0qBnYnOTwazkWv3W9L0CYiRJPBhEvDuZoQQZW-CBmvVAG68i7uusBA1Sui7f9DHXzdRa5UeYIbOpXv1XlSes0pQUopUDYts-QiVRgu90akEOpPsM4ePM4fERPgT12oMQa6-X_8_e_Vrzr4_YjegbNwEZ8d9DYU5yA6g9i4ED91DkjGS-764z4bcV7Cc-iK5vTn-oAen-0agfwEYxAde</recordid><startdate>20130611</startdate><enddate>20130611</enddate><creator>Hwang, Michael S</creator><creator>Yu, Nancy</creator><creator>Stinson, Susanna Y</creator><creator>Yue, Peng</creator><creator>Newman, Robert J</creator><creator>Allan, Bernard B</creator><creator>Dornan, David</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>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20130611</creationdate><title>miR-221/222 targets adiponectin receptor 1 to promote the epithelial-to-mesenchymal transition in breast cancer</title><author>Hwang, Michael S ; Yu, Nancy ; Stinson, Susanna Y ; Yue, Peng ; Newman, Robert J ; Allan, Bernard B ; Dornan, David</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-bb0a61245795b9288dfe168c8669f4c78df26946b6f135f6dd3fe016e7331dd83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>3' Untranslated regions</topic><topic>Aberration</topic><topic>Activation</topic><topic>Adiponectin</topic><topic>Apoptosis</topic><topic>Biology</topic><topic>Biotechnology</topic><topic>Blotting, Western</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - metabolism</topic><topic>Cancer</topic><topic>Cell Line, Tumor</topic><topic>Comparative analysis</topic><topic>Depletion</topic><topic>Development and progression</topic><topic>Epithelial-Mesenchymal Transition - genetics</topic><topic>Epithelial-Mesenchymal Transition - physiology</topic><topic>Female</topic><topic>Fluorescent Antibody Technique</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Neoplastic - genetics</topic><topic>Gene Expression Regulation, Neoplastic - physiology</topic><topic>Humans</topic><topic>Insulin resistance</topic><topic>Interleukin 6</topic><topic>Kinases</topic><topic>Medicine</topic><topic>Mesenchyme</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>MicroRNA</topic><topic>MicroRNAs</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>miRNA</topic><topic>Molecular biology</topic><topic>NF-κB protein</topic><topic>Pathogenesis</topic><topic>Phosphorylation</topic><topic>Physiological aspects</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Receptors, Adiponectin - genetics</topic><topic>Receptors, Adiponectin - metabolism</topic><topic>Rodents</topic><topic>siRNA</topic><topic>Stat3 protein</topic><topic>Stem cells</topic><topic>Transcription</topic><topic>Transcription factors</topic><topic>Tricho-rhino-phalangeal syndrome</topic><topic>Tumor cell lines</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hwang, Michael S</creatorcontrib><creatorcontrib>Yu, Nancy</creatorcontrib><creatorcontrib>Stinson, Susanna Y</creatorcontrib><creatorcontrib>Yue, Peng</creatorcontrib><creatorcontrib>Newman, Robert J</creatorcontrib><creatorcontrib>Allan, Bernard B</creatorcontrib><creatorcontrib>Dornan, David</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hwang, Michael S</au><au>Yu, Nancy</au><au>Stinson, Susanna Y</au><au>Yue, Peng</au><au>Newman, Robert J</au><au>Allan, Bernard B</au><au>Dornan, David</au><au>Katz, Elad</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>miR-221/222 targets adiponectin receptor 1 to promote the epithelial-to-mesenchymal transition in breast cancer</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-06-11</date><risdate>2013</risdate><volume>8</volume><issue>6</issue><spage>e66502</spage><epage>e66502</epage><pages>e66502-e66502</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The epithelial-to-mesenchymal transition (EMT) is a highly conserved physiological program involved in development and tissue repair; however, its aberrant activation has been implicated in accelerating the progression of a variety of cancers. In breast cancer, the microRNAs (miRNAs) miR-221 and miR-222 (miR-221/222) are differentially expressed in the clinically more aggressive basal-like subtype compared to luminal subtype of breast cancer and upregulation of miR-221/222 induces the EMT by targeting the 3' untranslated region (3'UTR) of the GATA family transcriptional repressor TRPS1 (tricho-rhino-phalangeal syndrome type 1). The complete mechanism through which miR-221/222 promotes the EMT, however, is not fully understood. We identified adiponectin receptor 1 (ADIPOR1), a receptor for the adipocytokine adiponectin, as a direct target of miR-221/222. ADIPOR1 is expressed at higher levels in the luminal compared to the basal-like subtype of breast cancer cell lines, which can be reduced by miR-221/222 targeting of its 3'UTR. In addition, miR-221/222 were negatively correlated with ADIPOR1 expression across breast cancer cell lines and tumors. ADIPOR1 depletion by siRNA in MCF10A cells induced the EMT and increased cell invasion. Depletion of ADIPOR1 by siRNA induced activation of the canonical nuclear factor-kappaB (NF-κB) and subsequent phosphorylation of signal transducer and activator of transcription 3 (STAT3) in an interleukin 6 (IL6)-dependent manner. Finally, overexpression of ADIPOR1 in the basal-like cell line, MDA-MB-231, attenuated cell invasion and promoted the mesenchymal-to-epithelial transition (MET). We conclude that ADIPOR1 negatively regulates EMT in breast cancer and provides an additional node by which miR-221/222 induces the EMT. These results suggest that ADIPOR1 may play an important role in breast cancer progression and metastasis, and could potentially offer an alternative therapeutic strategy for basal-like breast cancer patients.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23776679</pmid><doi>10.1371/journal.pone.0066502</doi><tpages>e66502</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2013-06, Vol.8 (6), p.e66502-e66502 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1366648246 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | 3' Untranslated regions Aberration Activation Adiponectin Apoptosis Biology Biotechnology Blotting, Western Breast cancer Breast Neoplasms - genetics Breast Neoplasms - metabolism Cancer Cell Line, Tumor Comparative analysis Depletion Development and progression Epithelial-Mesenchymal Transition - genetics Epithelial-Mesenchymal Transition - physiology Female Fluorescent Antibody Technique Gene expression Gene Expression Regulation, Neoplastic - genetics Gene Expression Regulation, Neoplastic - physiology Humans Insulin resistance Interleukin 6 Kinases Medicine Mesenchyme Metastases Metastasis MicroRNA MicroRNAs MicroRNAs - genetics MicroRNAs - metabolism miRNA Molecular biology NF-κB protein Pathogenesis Phosphorylation Physiological aspects Real-Time Polymerase Chain Reaction Receptors, Adiponectin - genetics Receptors, Adiponectin - metabolism Rodents siRNA Stat3 protein Stem cells Transcription Transcription factors Tricho-rhino-phalangeal syndrome Tumor cell lines Tumors |
| title | miR-221/222 targets adiponectin receptor 1 to promote the epithelial-to-mesenchymal transition in breast cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-31T21%3A54%3A13IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=miR-221/222%20targets%20adiponectin%20receptor%201%20to%20promote%20the%20epithelial-to-mesenchymal%20transition%20in%20breast%20cancer&rft.jtitle=PloS%20one&rft.au=Hwang,%20Michael%20S&rft.date=2013-06-11&rft.volume=8&rft.issue=6&rft.spage=e66502&rft.epage=e66502&rft.pages=e66502-e66502&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0066502&rft_dat=%3Cgale_plos_%3EA478325805%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1366648246&rft_id=info:pmid/23776679&rft_galeid=A478325805&rft_doaj_id=oai_doaj_org_article_630e56cb583c4337b432db448afc9f31&rfr_iscdi=true |