Epigenetic silencing of miR-145-5p contributes to brain metastasis
Brain metastasis is a major cause of morbidity and mortality of lung cancer patients. We assessed whether aberrant expression of specific microRNAs could contribute to brain metastasis. Comparison of primary lung tumors and their matched metastatic brain disseminations identified shared patterns of...
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| Veröffentlicht in: | Oncotarget 2015-11, Vol.6 (34), p.35183-35201 |
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| creator | Donzelli, Sara Mori, Federica Bellissimo, Teresa Sacconi, Andrea Casini, Beatrice Frixa, Tania Roscilli, Giuseppe Aurisicchio, Luigi Facciolo, Francesco Pompili, Alfredo Carosi, Maria Antonia Pescarmona, Edoardo Segatto, Oreste Pond, Greg Muti, Paola Telera, Stefano Strano, Sabrina Yarden, Yosef Blandino, Giovanni |
| description | Brain metastasis is a major cause of morbidity and mortality of lung cancer patients. We assessed whether aberrant expression of specific microRNAs could contribute to brain metastasis. Comparison of primary lung tumors and their matched metastatic brain disseminations identified shared patterns of several microRNAs, including common down-regulation of miR-145-5p. Down-regulation was attributed to methylation of miR-145's promoter and affiliated elevation of several protein targets, such as EGFR, OCT-4, MUC-1, c-MYC and, interestingly, tumor protein D52 (TPD52). In line with these observations, restored expression of miR-145-5p and selective depletion of individual targets markedly reduced in vitro and in vivo cancer cell migration. In aggregate, our results attribute to miR-145-5p and its direct targets pivotal roles in malignancy progression and in metastasis. |
| doi_str_mv | 10.18632/oncotarget.5930 |
| format | Article |
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We assessed whether aberrant expression of specific microRNAs could contribute to brain metastasis. Comparison of primary lung tumors and their matched metastatic brain disseminations identified shared patterns of several microRNAs, including common down-regulation of miR-145-5p. Down-regulation was attributed to methylation of miR-145's promoter and affiliated elevation of several protein targets, such as EGFR, OCT-4, MUC-1, c-MYC and, interestingly, tumor protein D52 (TPD52). In line with these observations, restored expression of miR-145-5p and selective depletion of individual targets markedly reduced in vitro and in vivo cancer cell migration. In aggregate, our results attribute to miR-145-5p and its direct targets pivotal roles in malignancy progression and in metastasis.</description><identifier>ISSN: 1949-2553</identifier><identifier>EISSN: 1949-2553</identifier><identifier>DOI: 10.18632/oncotarget.5930</identifier><identifier>PMID: 26440147</identifier><language>eng</language><publisher>United States: Impact Journals LLC</publisher><subject>Animals ; Brain Neoplasms - genetics ; Brain Neoplasms - metabolism ; Brain Neoplasms - secondary ; Cell Line, Tumor ; Cell Movement - physiology ; CpG Islands ; DNA Methylation ; Down-Regulation ; Epigenesis, Genetic ; Gene Silencing ; Heterografts ; Humans ; Lung Neoplasms - genetics ; Lung Neoplasms - metabolism ; Lung Neoplasms - pathology ; Mice ; Mice, Nude ; MicroRNAs - biosynthesis ; MicroRNAs - genetics ; MicroRNAs - metabolism ; Neoplasm Metastasis ; Priority Research Paper ; Signal Transduction</subject><ispartof>Oncotarget, 2015-11, Vol.6 (34), p.35183-35201</ispartof><rights>Copyright: © 2015 Donzelli et al. 2015</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c462t-ab4b795f78eea9463c3b0005554b6da822f150dafcee76529880f11df56a6b613</citedby><cites>FETCH-LOGICAL-c462t-ab4b795f78eea9463c3b0005554b6da822f150dafcee76529880f11df56a6b613</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/PMC4742098/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4742098/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26440147$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Donzelli, Sara</creatorcontrib><creatorcontrib>Mori, Federica</creatorcontrib><creatorcontrib>Bellissimo, Teresa</creatorcontrib><creatorcontrib>Sacconi, Andrea</creatorcontrib><creatorcontrib>Casini, Beatrice</creatorcontrib><creatorcontrib>Frixa, Tania</creatorcontrib><creatorcontrib>Roscilli, Giuseppe</creatorcontrib><creatorcontrib>Aurisicchio, Luigi</creatorcontrib><creatorcontrib>Facciolo, Francesco</creatorcontrib><creatorcontrib>Pompili, Alfredo</creatorcontrib><creatorcontrib>Carosi, Maria Antonia</creatorcontrib><creatorcontrib>Pescarmona, Edoardo</creatorcontrib><creatorcontrib>Segatto, Oreste</creatorcontrib><creatorcontrib>Pond, Greg</creatorcontrib><creatorcontrib>Muti, Paola</creatorcontrib><creatorcontrib>Telera, Stefano</creatorcontrib><creatorcontrib>Strano, Sabrina</creatorcontrib><creatorcontrib>Yarden, Yosef</creatorcontrib><creatorcontrib>Blandino, Giovanni</creatorcontrib><title>Epigenetic silencing of miR-145-5p contributes to brain metastasis</title><title>Oncotarget</title><addtitle>Oncotarget</addtitle><description>Brain metastasis is a major cause of morbidity and mortality of lung cancer patients. We assessed whether aberrant expression of specific microRNAs could contribute to brain metastasis. Comparison of primary lung tumors and their matched metastatic brain disseminations identified shared patterns of several microRNAs, including common down-regulation of miR-145-5p. Down-regulation was attributed to methylation of miR-145's promoter and affiliated elevation of several protein targets, such as EGFR, OCT-4, MUC-1, c-MYC and, interestingly, tumor protein D52 (TPD52). In line with these observations, restored expression of miR-145-5p and selective depletion of individual targets markedly reduced in vitro and in vivo cancer cell migration. In aggregate, our results attribute to miR-145-5p and its direct targets pivotal roles in malignancy progression and in metastasis.</description><subject>Animals</subject><subject>Brain Neoplasms - genetics</subject><subject>Brain Neoplasms - metabolism</subject><subject>Brain Neoplasms - secondary</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement - physiology</subject><subject>CpG Islands</subject><subject>DNA Methylation</subject><subject>Down-Regulation</subject><subject>Epigenesis, Genetic</subject><subject>Gene Silencing</subject><subject>Heterografts</subject><subject>Humans</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - metabolism</subject><subject>Lung Neoplasms - pathology</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>MicroRNAs - biosynthesis</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>Neoplasm Metastasis</subject><subject>Priority Research Paper</subject><subject>Signal Transduction</subject><issn>1949-2553</issn><issn>1949-2553</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUE1Lw0AQXUSxpfbuSXL0krrfyV4ELfUDCoLoedlsJ3ElydbsRvDfm9pa6zAwA_Pem8dD6JzgGcklo1e-tT6aroI4E4rhIzQmiquUCsGOD_YRmobwjocSPMupOkUjKjnHhGdjdLtYuwpaiM4mwdXQWtdWiS-Txj2nhItUrBPr29i5oo8QkuiTojOuTRqIJgztwhk6KU0dYLqbE_R6t3iZP6TLp_vH-c0ytVzSmJqCF5kSZZYDGMUls6zYeBKCF3JlckpLIvDKlBYgk4KqPMclIatSSCMLSdgEXW91133RwMrC4MrUet25xnRf2hun_19a96Yr_6l5xilW-SBwuRPo_EcPIerGBQt1bVrwfdAkY4IxoTgfoHgLtZ0PoYNy_4Zg_ZO-_ktfb9IfKBeH9vaE36zZN6xJg4E</recordid><startdate>20151103</startdate><enddate>20151103</enddate><creator>Donzelli, Sara</creator><creator>Mori, Federica</creator><creator>Bellissimo, Teresa</creator><creator>Sacconi, Andrea</creator><creator>Casini, Beatrice</creator><creator>Frixa, Tania</creator><creator>Roscilli, Giuseppe</creator><creator>Aurisicchio, Luigi</creator><creator>Facciolo, Francesco</creator><creator>Pompili, Alfredo</creator><creator>Carosi, Maria Antonia</creator><creator>Pescarmona, Edoardo</creator><creator>Segatto, Oreste</creator><creator>Pond, Greg</creator><creator>Muti, Paola</creator><creator>Telera, Stefano</creator><creator>Strano, Sabrina</creator><creator>Yarden, Yosef</creator><creator>Blandino, Giovanni</creator><general>Impact Journals LLC</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20151103</creationdate><title>Epigenetic silencing of miR-145-5p contributes to brain metastasis</title><author>Donzelli, Sara ; Mori, Federica ; Bellissimo, Teresa ; Sacconi, Andrea ; Casini, Beatrice ; Frixa, Tania ; Roscilli, Giuseppe ; Aurisicchio, Luigi ; Facciolo, Francesco ; Pompili, Alfredo ; Carosi, Maria Antonia ; Pescarmona, Edoardo ; Segatto, Oreste ; Pond, Greg ; Muti, Paola ; Telera, Stefano ; Strano, Sabrina ; Yarden, Yosef ; Blandino, Giovanni</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c462t-ab4b795f78eea9463c3b0005554b6da822f150dafcee76529880f11df56a6b613</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Brain Neoplasms - genetics</topic><topic>Brain Neoplasms - metabolism</topic><topic>Brain Neoplasms - secondary</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement - physiology</topic><topic>CpG Islands</topic><topic>DNA Methylation</topic><topic>Down-Regulation</topic><topic>Epigenesis, Genetic</topic><topic>Gene Silencing</topic><topic>Heterografts</topic><topic>Humans</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - metabolism</topic><topic>Lung Neoplasms - pathology</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>MicroRNAs - biosynthesis</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>Neoplasm Metastasis</topic><topic>Priority Research Paper</topic><topic>Signal Transduction</topic><toplevel>online_resources</toplevel><creatorcontrib>Donzelli, Sara</creatorcontrib><creatorcontrib>Mori, Federica</creatorcontrib><creatorcontrib>Bellissimo, Teresa</creatorcontrib><creatorcontrib>Sacconi, Andrea</creatorcontrib><creatorcontrib>Casini, Beatrice</creatorcontrib><creatorcontrib>Frixa, Tania</creatorcontrib><creatorcontrib>Roscilli, Giuseppe</creatorcontrib><creatorcontrib>Aurisicchio, Luigi</creatorcontrib><creatorcontrib>Facciolo, Francesco</creatorcontrib><creatorcontrib>Pompili, Alfredo</creatorcontrib><creatorcontrib>Carosi, Maria Antonia</creatorcontrib><creatorcontrib>Pescarmona, Edoardo</creatorcontrib><creatorcontrib>Segatto, Oreste</creatorcontrib><creatorcontrib>Pond, Greg</creatorcontrib><creatorcontrib>Muti, Paola</creatorcontrib><creatorcontrib>Telera, Stefano</creatorcontrib><creatorcontrib>Strano, Sabrina</creatorcontrib><creatorcontrib>Yarden, Yosef</creatorcontrib><creatorcontrib>Blandino, Giovanni</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Oncotarget</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Donzelli, Sara</au><au>Mori, Federica</au><au>Bellissimo, Teresa</au><au>Sacconi, Andrea</au><au>Casini, Beatrice</au><au>Frixa, Tania</au><au>Roscilli, Giuseppe</au><au>Aurisicchio, Luigi</au><au>Facciolo, Francesco</au><au>Pompili, Alfredo</au><au>Carosi, Maria Antonia</au><au>Pescarmona, Edoardo</au><au>Segatto, Oreste</au><au>Pond, Greg</au><au>Muti, Paola</au><au>Telera, Stefano</au><au>Strano, Sabrina</au><au>Yarden, Yosef</au><au>Blandino, Giovanni</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Epigenetic silencing of miR-145-5p contributes to brain metastasis</atitle><jtitle>Oncotarget</jtitle><addtitle>Oncotarget</addtitle><date>2015-11-03</date><risdate>2015</risdate><volume>6</volume><issue>34</issue><spage>35183</spage><epage>35201</epage><pages>35183-35201</pages><issn>1949-2553</issn><eissn>1949-2553</eissn><abstract>Brain metastasis is a major cause of morbidity and mortality of lung cancer patients. 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| identifier | ISSN: 1949-2553 |
| ispartof | Oncotarget, 2015-11, Vol.6 (34), p.35183-35201 |
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| subjects | Animals Brain Neoplasms - genetics Brain Neoplasms - metabolism Brain Neoplasms - secondary Cell Line, Tumor Cell Movement - physiology CpG Islands DNA Methylation Down-Regulation Epigenesis, Genetic Gene Silencing Heterografts Humans Lung Neoplasms - genetics Lung Neoplasms - metabolism Lung Neoplasms - pathology Mice Mice, Nude MicroRNAs - biosynthesis MicroRNAs - genetics MicroRNAs - metabolism Neoplasm Metastasis Priority Research Paper Signal Transduction |
| title | Epigenetic silencing of miR-145-5p contributes to brain metastasis |
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