Transcription signatures encoded by ultraconserved genomic regions in human prostate cancer
Ultraconserved regions (UCR) are genomic segments of more than 200 base pairs that are evolutionarily conserved among mammalian species. They are thought to have functions as transcriptional enhancers and regulators of alternative splicing. Recently, it was shown that numerous RNAs are transcribed f...
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| Veröffentlicht in: | Molecular cancer 2013-02, Vol.12 (1), p.13-13, Article 13 |
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| creator | Hudson, Robert S Yi, Ming Volfovsky, Natalia Prueitt, Robyn L Esposito, Dominic Volinia, Stefano Liu, Chang-Gong Schetter, Aaron J Van Roosbroeck, Katrien Stephens, Robert M Calin, George A Croce, Carlo M Ambs, Stefan |
| description | Ultraconserved regions (UCR) are genomic segments of more than 200 base pairs that are evolutionarily conserved among mammalian species. They are thought to have functions as transcriptional enhancers and regulators of alternative splicing. Recently, it was shown that numerous RNAs are transcribed from these regions. These UCR-encoded transcripts (ucRNAs) were found to be expressed in a tissue- and disease-specific manner and may interfere with the function of other RNAs through RNA: RNA interactions. We hypothesized that ucRNAs have unidentified roles in the pathogenesis of human prostate cancer. In a pilot study, we examined ucRNA expression profiles in human prostate tumors.
Using a custom microarray with 962 probesets representing sense and antisense sequences for the 481 human UCRs, we examined ucRNA expression in resected, fresh-frozen human prostate tissues (57 tumors, 7 non-cancerous prostate tissues) and in cultured prostate cancer cells treated with either epigenetic drugs (the hypomethylating agent, 5-Aza 2'deoxycytidine, and the histone deacetylase inhibitor, trichostatin A) or a synthetic androgen, R1881. Expression of selected ucRNAs was also assessed by qRT-PCR and NanoString®-based assays. Because ucRNAs may function as RNAs that target protein-coding genes through direct and inhibitory RNA: RNA interactions, computational analyses were applied to identify candidate ucRNA:mRNA binding pairs.
We observed altered ucRNA expression in prostate cancer (e.g., uc.106+, uc.477+, uc.363 + A, uc.454 + A) and found that these ucRNAs were associated with cancer development, Gleason score, and extraprostatic extension after controlling for false discovery (false discovery rate < 5% for many of the transcripts). We also identified several ucRNAs that were responsive to treatment with either epigenetic drugs or androgen (R1881). For example, experiments with LNCaP human prostate cancer cells showed that uc.287+ is induced by R1881 (P < 0.05) whereas uc.283 + A was up-regulated following treatment with combined 5-Aza 2'deoxycytidine and trichostatin A (P < 0.05). Additional computational analyses predicted RNA loop-loop interactions of 302 different sense and antisense ucRNAs with 1058 different mRNAs, inferring possible functions of ucRNAs via direct interactions with mRNAs.
This first study of ucRNA expression in human prostate cancer indicates an altered transcript expression in the disease. |
| doi_str_mv | 10.1186/1476-4598-12-13 |
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| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3626580</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A534664325</galeid><sourcerecordid>A534664325</sourcerecordid><originalsourceid>FETCH-LOGICAL-b646t-be3ca5d3497f545c619edaa3c551ff4d5c6bf7cfa9d61f7b30658ef09901d8413</originalsourceid><addsrcrecordid>eNp1kk1v1DAQhi0EoqVw5oYsceklrR1_JLkglapApUpcyomD5djj1FViL3ZSqf8ehy1LtyrywdbMO49m3jFC7yk5obSVp5Q3suKiaytaV5S9QIe7yMtH7wP0JudbQmjTNvw1OqgZJ13TsEP08zrpkE3ym9nHgLMfgp6XBBlDMNGCxf09XsY5aRNDhnRXIgOEOHmDEwylJmMf8M0y6YA3KeZZz4CNDgbSW_TK6THDu4f7CP34cnF9_q26-v718vzsquoll3PVAzNaWMa7xgkujKQdWK2ZEYI6x22J9K4xTndWUtf0jEjRgiNdR6htOWVH6NOWu1n6CayBUNod1Sb5Sad7FbVX-5ngb9QQ7xSTdUGRAvi8BfQ-_gewnzFxUqu5ajVX0VpRViDHD12k-GuBPKvJZwPjqAPEJRd9V0smOtIW6ccn0tu4pFA8KqBaNm1d1-KfatAjKB9cXLewQtWZYFxKzv6oTp5RlWOh7CgGcL7E9wpOtwWmbCsncLs5KVHrp3pmsg-P_d3p__4i9htbScj_</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1326782225</pqid></control><display><type>article</type><title>Transcription signatures encoded by ultraconserved genomic regions in human prostate cancer</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>SpringerNature Journals</source><source>PubMed Central Open Access</source><source>Springer Nature OA Free Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Hudson, Robert S ; Yi, Ming ; Volfovsky, Natalia ; Prueitt, Robyn L ; Esposito, Dominic ; Volinia, Stefano ; Liu, Chang-Gong ; Schetter, Aaron J ; Van Roosbroeck, Katrien ; Stephens, Robert M ; Calin, George A ; Croce, Carlo M ; Ambs, Stefan</creator><creatorcontrib>Hudson, Robert S ; Yi, Ming ; Volfovsky, Natalia ; Prueitt, Robyn L ; Esposito, Dominic ; Volinia, Stefano ; Liu, Chang-Gong ; Schetter, Aaron J ; Van Roosbroeck, Katrien ; Stephens, Robert M ; Calin, George A ; Croce, Carlo M ; Ambs, Stefan</creatorcontrib><description>Ultraconserved regions (UCR) are genomic segments of more than 200 base pairs that are evolutionarily conserved among mammalian species. They are thought to have functions as transcriptional enhancers and regulators of alternative splicing. Recently, it was shown that numerous RNAs are transcribed from these regions. These UCR-encoded transcripts (ucRNAs) were found to be expressed in a tissue- and disease-specific manner and may interfere with the function of other RNAs through RNA: RNA interactions. We hypothesized that ucRNAs have unidentified roles in the pathogenesis of human prostate cancer. In a pilot study, we examined ucRNA expression profiles in human prostate tumors.
Using a custom microarray with 962 probesets representing sense and antisense sequences for the 481 human UCRs, we examined ucRNA expression in resected, fresh-frozen human prostate tissues (57 tumors, 7 non-cancerous prostate tissues) and in cultured prostate cancer cells treated with either epigenetic drugs (the hypomethylating agent, 5-Aza 2'deoxycytidine, and the histone deacetylase inhibitor, trichostatin A) or a synthetic androgen, R1881. Expression of selected ucRNAs was also assessed by qRT-PCR and NanoString®-based assays. Because ucRNAs may function as RNAs that target protein-coding genes through direct and inhibitory RNA: RNA interactions, computational analyses were applied to identify candidate ucRNA:mRNA binding pairs.
We observed altered ucRNA expression in prostate cancer (e.g., uc.106+, uc.477+, uc.363 + A, uc.454 + A) and found that these ucRNAs were associated with cancer development, Gleason score, and extraprostatic extension after controlling for false discovery (false discovery rate < 5% for many of the transcripts). We also identified several ucRNAs that were responsive to treatment with either epigenetic drugs or androgen (R1881). For example, experiments with LNCaP human prostate cancer cells showed that uc.287+ is induced by R1881 (P < 0.05) whereas uc.283 + A was up-regulated following treatment with combined 5-Aza 2'deoxycytidine and trichostatin A (P < 0.05). Additional computational analyses predicted RNA loop-loop interactions of 302 different sense and antisense ucRNAs with 1058 different mRNAs, inferring possible functions of ucRNAs via direct interactions with mRNAs.
This first study of ucRNA expression in human prostate cancer indicates an altered transcript expression in the disease.</description><identifier>ISSN: 1476-4598</identifier><identifier>EISSN: 1476-4598</identifier><identifier>DOI: 10.1186/1476-4598-12-13</identifier><identifier>PMID: 23409773</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Adenocarcinoma - genetics ; Adenocarcinoma - metabolism ; Aged ; Alternative splicing ; Analysis ; Azacitidine - analogs & derivatives ; Azacitidine - pharmacology ; Cancer ; Case-Control Studies ; Cell culture ; Cell Line, Tumor ; Conserved Sequence ; Development and progression ; Drug therapy ; Epigenesis, Genetic - drug effects ; Epigenetic inheritance ; Epigenetics ; Gene Expression ; Gene Expression Regulation, Neoplastic ; Genes ; Genetic aspects ; Genetic research ; Genetic transcription ; Genetics ; Genome, Human ; Genomes ; Histone Deacetylase Inhibitors - pharmacology ; Humans ; Hydroxamic Acids - pharmacology ; Liver cancer ; Male ; Medical research ; Messenger RNA ; Metribolone - pharmacology ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; Prostate - metabolism ; Prostate cancer ; Prostatic Neoplasms - genetics ; Prostatic Neoplasms - metabolism ; Proteins ; RNA, Messenger - genetics ; RNA, Neoplasm - genetics ; RNA, Neoplasm - metabolism ; RNA, Untranslated - genetics ; RNA, Untranslated - metabolism ; Software ; Statistical analysis ; Testosterone Congeners - pharmacology ; Transcriptome ; Wildlife conservation</subject><ispartof>Molecular cancer, 2013-02, Vol.12 (1), p.13-13, Article 13</ispartof><rights>COPYRIGHT 2013 BioMed Central Ltd.</rights><rights>2013 Hudson et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</rights><rights>Copyright © 2013 Hudson et al.; licensee BioMed Central Ltd. 2013 Hudson et al.; licensee BioMed Central Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b646t-be3ca5d3497f545c619edaa3c551ff4d5c6bf7cfa9d61f7b30658ef09901d8413</citedby><cites>FETCH-LOGICAL-b646t-be3ca5d3497f545c619edaa3c551ff4d5c6bf7cfa9d61f7b30658ef09901d8413</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/PMC3626580/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3626580/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23409773$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hudson, Robert S</creatorcontrib><creatorcontrib>Yi, Ming</creatorcontrib><creatorcontrib>Volfovsky, Natalia</creatorcontrib><creatorcontrib>Prueitt, Robyn L</creatorcontrib><creatorcontrib>Esposito, Dominic</creatorcontrib><creatorcontrib>Volinia, Stefano</creatorcontrib><creatorcontrib>Liu, Chang-Gong</creatorcontrib><creatorcontrib>Schetter, Aaron J</creatorcontrib><creatorcontrib>Van Roosbroeck, Katrien</creatorcontrib><creatorcontrib>Stephens, Robert M</creatorcontrib><creatorcontrib>Calin, George A</creatorcontrib><creatorcontrib>Croce, Carlo M</creatorcontrib><creatorcontrib>Ambs, Stefan</creatorcontrib><title>Transcription signatures encoded by ultraconserved genomic regions in human prostate cancer</title><title>Molecular cancer</title><addtitle>Mol Cancer</addtitle><description>Ultraconserved regions (UCR) are genomic segments of more than 200 base pairs that are evolutionarily conserved among mammalian species. They are thought to have functions as transcriptional enhancers and regulators of alternative splicing. Recently, it was shown that numerous RNAs are transcribed from these regions. These UCR-encoded transcripts (ucRNAs) were found to be expressed in a tissue- and disease-specific manner and may interfere with the function of other RNAs through RNA: RNA interactions. We hypothesized that ucRNAs have unidentified roles in the pathogenesis of human prostate cancer. In a pilot study, we examined ucRNA expression profiles in human prostate tumors.
Using a custom microarray with 962 probesets representing sense and antisense sequences for the 481 human UCRs, we examined ucRNA expression in resected, fresh-frozen human prostate tissues (57 tumors, 7 non-cancerous prostate tissues) and in cultured prostate cancer cells treated with either epigenetic drugs (the hypomethylating agent, 5-Aza 2'deoxycytidine, and the histone deacetylase inhibitor, trichostatin A) or a synthetic androgen, R1881. Expression of selected ucRNAs was also assessed by qRT-PCR and NanoString®-based assays. Because ucRNAs may function as RNAs that target protein-coding genes through direct and inhibitory RNA: RNA interactions, computational analyses were applied to identify candidate ucRNA:mRNA binding pairs.
We observed altered ucRNA expression in prostate cancer (e.g., uc.106+, uc.477+, uc.363 + A, uc.454 + A) and found that these ucRNAs were associated with cancer development, Gleason score, and extraprostatic extension after controlling for false discovery (false discovery rate < 5% for many of the transcripts). We also identified several ucRNAs that were responsive to treatment with either epigenetic drugs or androgen (R1881). For example, experiments with LNCaP human prostate cancer cells showed that uc.287+ is induced by R1881 (P < 0.05) whereas uc.283 + A was up-regulated following treatment with combined 5-Aza 2'deoxycytidine and trichostatin A (P < 0.05). Additional computational analyses predicted RNA loop-loop interactions of 302 different sense and antisense ucRNAs with 1058 different mRNAs, inferring possible functions of ucRNAs via direct interactions with mRNAs.
This first study of ucRNA expression in human prostate cancer indicates an altered transcript expression in the disease.</description><subject>Adenocarcinoma - genetics</subject><subject>Adenocarcinoma - metabolism</subject><subject>Aged</subject><subject>Alternative splicing</subject><subject>Analysis</subject><subject>Azacitidine - analogs & derivatives</subject><subject>Azacitidine - pharmacology</subject><subject>Cancer</subject><subject>Case-Control Studies</subject><subject>Cell culture</subject><subject>Cell Line, Tumor</subject><subject>Conserved Sequence</subject><subject>Development and progression</subject><subject>Drug therapy</subject><subject>Epigenesis, Genetic - drug effects</subject><subject>Epigenetic inheritance</subject><subject>Epigenetics</subject><subject>Gene Expression</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic research</subject><subject>Genetic transcription</subject><subject>Genetics</subject><subject>Genome, Human</subject><subject>Genomes</subject><subject>Histone Deacetylase Inhibitors - pharmacology</subject><subject>Humans</subject><subject>Hydroxamic Acids - pharmacology</subject><subject>Liver cancer</subject><subject>Male</subject><subject>Medical research</subject><subject>Messenger RNA</subject><subject>Metribolone - pharmacology</subject><subject>Middle Aged</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Prostate - metabolism</subject><subject>Prostate cancer</subject><subject>Prostatic Neoplasms - genetics</subject><subject>Prostatic Neoplasms - metabolism</subject><subject>Proteins</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Neoplasm - genetics</subject><subject>RNA, Neoplasm - metabolism</subject><subject>RNA, Untranslated - genetics</subject><subject>RNA, Untranslated - metabolism</subject><subject>Software</subject><subject>Statistical analysis</subject><subject>Testosterone Congeners - pharmacology</subject><subject>Transcriptome</subject><subject>Wildlife conservation</subject><issn>1476-4598</issn><issn>1476-4598</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</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><recordid>eNp1kk1v1DAQhi0EoqVw5oYsceklrR1_JLkglapApUpcyomD5djj1FViL3ZSqf8ehy1LtyrywdbMO49m3jFC7yk5obSVp5Q3suKiaytaV5S9QIe7yMtH7wP0JudbQmjTNvw1OqgZJ13TsEP08zrpkE3ym9nHgLMfgp6XBBlDMNGCxf09XsY5aRNDhnRXIgOEOHmDEwylJmMf8M0y6YA3KeZZz4CNDgbSW_TK6THDu4f7CP34cnF9_q26-v718vzsquoll3PVAzNaWMa7xgkujKQdWK2ZEYI6x22J9K4xTndWUtf0jEjRgiNdR6htOWVH6NOWu1n6CayBUNod1Sb5Sad7FbVX-5ngb9QQ7xSTdUGRAvi8BfQ-_gewnzFxUqu5ajVX0VpRViDHD12k-GuBPKvJZwPjqAPEJRd9V0smOtIW6ccn0tu4pFA8KqBaNm1d1-KfatAjKB9cXLewQtWZYFxKzv6oTp5RlWOh7CgGcL7E9wpOtwWmbCsncLs5KVHrp3pmsg-P_d3p__4i9htbScj_</recordid><startdate>20130214</startdate><enddate>20130214</enddate><creator>Hudson, Robert S</creator><creator>Yi, Ming</creator><creator>Volfovsky, Natalia</creator><creator>Prueitt, Robyn L</creator><creator>Esposito, Dominic</creator><creator>Volinia, Stefano</creator><creator>Liu, Chang-Gong</creator><creator>Schetter, Aaron J</creator><creator>Van Roosbroeck, Katrien</creator><creator>Stephens, Robert M</creator><creator>Calin, George A</creator><creator>Croce, Carlo M</creator><creator>Ambs, Stefan</creator><general>BioMed Central Ltd</general><general>BioMed Central</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>3V.</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20130214</creationdate><title>Transcription signatures encoded by ultraconserved genomic regions in human prostate cancer</title><author>Hudson, Robert S ; Yi, Ming ; Volfovsky, Natalia ; Prueitt, Robyn L ; Esposito, Dominic ; Volinia, Stefano ; Liu, Chang-Gong ; Schetter, Aaron J ; Van Roosbroeck, Katrien ; Stephens, Robert M ; Calin, George A ; Croce, Carlo M ; Ambs, Stefan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b646t-be3ca5d3497f545c619edaa3c551ff4d5c6bf7cfa9d61f7b30658ef09901d8413</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adenocarcinoma - genetics</topic><topic>Adenocarcinoma - metabolism</topic><topic>Aged</topic><topic>Alternative splicing</topic><topic>Analysis</topic><topic>Azacitidine - analogs & derivatives</topic><topic>Azacitidine - pharmacology</topic><topic>Cancer</topic><topic>Case-Control Studies</topic><topic>Cell culture</topic><topic>Cell Line, Tumor</topic><topic>Conserved Sequence</topic><topic>Development and progression</topic><topic>Drug therapy</topic><topic>Epigenesis, Genetic - drug effects</topic><topic>Epigenetic inheritance</topic><topic>Epigenetics</topic><topic>Gene Expression</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genetic research</topic><topic>Genetic transcription</topic><topic>Genetics</topic><topic>Genome, Human</topic><topic>Genomes</topic><topic>Histone Deacetylase Inhibitors - pharmacology</topic><topic>Humans</topic><topic>Hydroxamic Acids - pharmacology</topic><topic>Liver cancer</topic><topic>Male</topic><topic>Medical research</topic><topic>Messenger RNA</topic><topic>Metribolone - pharmacology</topic><topic>Middle Aged</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Prostate - metabolism</topic><topic>Prostate cancer</topic><topic>Prostatic Neoplasms - genetics</topic><topic>Prostatic Neoplasms - metabolism</topic><topic>Proteins</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Neoplasm - genetics</topic><topic>RNA, Neoplasm - metabolism</topic><topic>RNA, Untranslated - genetics</topic><topic>RNA, Untranslated - metabolism</topic><topic>Software</topic><topic>Statistical analysis</topic><topic>Testosterone Congeners - pharmacology</topic><topic>Transcriptome</topic><topic>Wildlife conservation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hudson, Robert S</creatorcontrib><creatorcontrib>Yi, Ming</creatorcontrib><creatorcontrib>Volfovsky, Natalia</creatorcontrib><creatorcontrib>Prueitt, Robyn L</creatorcontrib><creatorcontrib>Esposito, Dominic</creatorcontrib><creatorcontrib>Volinia, Stefano</creatorcontrib><creatorcontrib>Liu, Chang-Gong</creatorcontrib><creatorcontrib>Schetter, Aaron J</creatorcontrib><creatorcontrib>Van Roosbroeck, Katrien</creatorcontrib><creatorcontrib>Stephens, Robert M</creatorcontrib><creatorcontrib>Calin, George A</creatorcontrib><creatorcontrib>Croce, Carlo M</creatorcontrib><creatorcontrib>Ambs, Stefan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</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>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hudson, Robert S</au><au>Yi, Ming</au><au>Volfovsky, Natalia</au><au>Prueitt, Robyn L</au><au>Esposito, Dominic</au><au>Volinia, Stefano</au><au>Liu, Chang-Gong</au><au>Schetter, Aaron J</au><au>Van Roosbroeck, Katrien</au><au>Stephens, Robert M</au><au>Calin, George A</au><au>Croce, Carlo M</au><au>Ambs, Stefan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Transcription signatures encoded by ultraconserved genomic regions in human prostate cancer</atitle><jtitle>Molecular cancer</jtitle><addtitle>Mol Cancer</addtitle><date>2013-02-14</date><risdate>2013</risdate><volume>12</volume><issue>1</issue><spage>13</spage><epage>13</epage><pages>13-13</pages><artnum>13</artnum><issn>1476-4598</issn><eissn>1476-4598</eissn><abstract>Ultraconserved regions (UCR) are genomic segments of more than 200 base pairs that are evolutionarily conserved among mammalian species. They are thought to have functions as transcriptional enhancers and regulators of alternative splicing. Recently, it was shown that numerous RNAs are transcribed from these regions. These UCR-encoded transcripts (ucRNAs) were found to be expressed in a tissue- and disease-specific manner and may interfere with the function of other RNAs through RNA: RNA interactions. We hypothesized that ucRNAs have unidentified roles in the pathogenesis of human prostate cancer. In a pilot study, we examined ucRNA expression profiles in human prostate tumors.
Using a custom microarray with 962 probesets representing sense and antisense sequences for the 481 human UCRs, we examined ucRNA expression in resected, fresh-frozen human prostate tissues (57 tumors, 7 non-cancerous prostate tissues) and in cultured prostate cancer cells treated with either epigenetic drugs (the hypomethylating agent, 5-Aza 2'deoxycytidine, and the histone deacetylase inhibitor, trichostatin A) or a synthetic androgen, R1881. Expression of selected ucRNAs was also assessed by qRT-PCR and NanoString®-based assays. Because ucRNAs may function as RNAs that target protein-coding genes through direct and inhibitory RNA: RNA interactions, computational analyses were applied to identify candidate ucRNA:mRNA binding pairs.
We observed altered ucRNA expression in prostate cancer (e.g., uc.106+, uc.477+, uc.363 + A, uc.454 + A) and found that these ucRNAs were associated with cancer development, Gleason score, and extraprostatic extension after controlling for false discovery (false discovery rate < 5% for many of the transcripts). We also identified several ucRNAs that were responsive to treatment with either epigenetic drugs or androgen (R1881). For example, experiments with LNCaP human prostate cancer cells showed that uc.287+ is induced by R1881 (P < 0.05) whereas uc.283 + A was up-regulated following treatment with combined 5-Aza 2'deoxycytidine and trichostatin A (P < 0.05). Additional computational analyses predicted RNA loop-loop interactions of 302 different sense and antisense ucRNAs with 1058 different mRNAs, inferring possible functions of ucRNAs via direct interactions with mRNAs.
This first study of ucRNA expression in human prostate cancer indicates an altered transcript expression in the disease.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>23409773</pmid><doi>10.1186/1476-4598-12-13</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adenocarcinoma - genetics Adenocarcinoma - metabolism Aged Alternative splicing Analysis Azacitidine - analogs & derivatives Azacitidine - pharmacology Cancer Case-Control Studies Cell culture Cell Line, Tumor Conserved Sequence Development and progression Drug therapy Epigenesis, Genetic - drug effects Epigenetic inheritance Epigenetics Gene Expression Gene Expression Regulation, Neoplastic Genes Genetic aspects Genetic research Genetic transcription Genetics Genome, Human Genomes Histone Deacetylase Inhibitors - pharmacology Humans Hydroxamic Acids - pharmacology Liver cancer Male Medical research Messenger RNA Metribolone - pharmacology Middle Aged Oligonucleotide Array Sequence Analysis Prostate - metabolism Prostate cancer Prostatic Neoplasms - genetics Prostatic Neoplasms - metabolism Proteins RNA, Messenger - genetics RNA, Neoplasm - genetics RNA, Neoplasm - metabolism RNA, Untranslated - genetics RNA, Untranslated - metabolism Software Statistical analysis Testosterone Congeners - pharmacology Transcriptome Wildlife conservation |
| title | Transcription signatures encoded by ultraconserved genomic regions in human prostate cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-22T19%3A35%3A35IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Transcription%20signatures%20encoded%20by%20ultraconserved%20genomic%20regions%20in%20human%20prostate%20cancer&rft.jtitle=Molecular%20cancer&rft.au=Hudson,%20Robert%20S&rft.date=2013-02-14&rft.volume=12&rft.issue=1&rft.spage=13&rft.epage=13&rft.pages=13-13&rft.artnum=13&rft.issn=1476-4598&rft.eissn=1476-4598&rft_id=info:doi/10.1186/1476-4598-12-13&rft_dat=%3Cgale_pubme%3EA534664325%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1326782225&rft_id=info:pmid/23409773&rft_galeid=A534664325&rfr_iscdi=true |