Genome-wide analysis reveals downregulation of miR-379/miR-656 cluster in human cancers
MicroRNAs (miRNAs) are non-uniformly distributed in genomes and ~30% of the miRNAs in the human genome are clustered. In this study we have focused on the imprinted miRNA cluster miR-379/miR-656 on 14q32.31 (hereafter C14) to test their coordinated function. We have analyzed expression profile of &g...
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| Veröffentlicht in: | Biology direct 2013-04, Vol.8 (1), p.10-10, Article 10 |
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| creator | Laddha, Saurabh V Nayak, Subhashree Paul, Deepanjan Reddy, Rajasekhara Sharma, Charu Jha, Prerana Hariharan, Manoj Agrawal, Anurag Chowdhury, Shantanu Sarkar, Chitra Mukhopadhyay, Arijit |
| description | MicroRNAs (miRNAs) are non-uniformly distributed in genomes and ~30% of the miRNAs in the human genome are clustered. In this study we have focused on the imprinted miRNA cluster miR-379/miR-656 on 14q32.31 (hereafter C14) to test their coordinated function. We have analyzed expression profile of >1000 human miRNAs in >1400 samples representing seven different human tissue types obtained from cancer patients along with matched and unmatched controls.
We found 68% of the miRNAs in this cluster to be significantly downregulated in glioblastoma multiforme (GBM), 61% downregulated in kidney renal clear cell carcinoma (KIRC), 46% in breast invasive carcinoma (BRCA) and 14% in ovarian serous cystadenocarcinoma (OV). On a genome-wide scale C14 miRNAs accounted for 12-30% of the total downregulated miRNAs in different cancers. Pathway enrichment for the predicted targets of C14 miRNA was significant for cancer pathways, especially Glioma (p< 3.77x10⁻⁶, FDR |
| doi_str_mv | 10.1186/1745-6150-8-10 |
| format | Article |
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We found 68% of the miRNAs in this cluster to be significantly downregulated in glioblastoma multiforme (GBM), 61% downregulated in kidney renal clear cell carcinoma (KIRC), 46% in breast invasive carcinoma (BRCA) and 14% in ovarian serous cystadenocarcinoma (OV). On a genome-wide scale C14 miRNAs accounted for 12-30% of the total downregulated miRNAs in different cancers. Pathway enrichment for the predicted targets of C14 miRNA was significant for cancer pathways, especially Glioma (p< 3.77x10⁻⁶, FDR<0.005). The observed downregulation was confirmed in GBM patients by real-time PCR, where 79% of C14 miRNAs (34/43) showed downregulation. In GBM samples, hypermethylation at C14 locus (p<0.003) and downregulation of MEF2, a crucial transcription factor for the cluster was observed which likely contribute to the observed downregulation of the entire miRNA cluster.
We provide compelling evidence that the entire C14 miRNA cluster is a tumor suppressor locus involved in multiple cancers, especially in GBM, and points toward a general mechanism of coordinated function for clustered miRNAs.</description><identifier>ISSN: 1745-6150</identifier><identifier>EISSN: 1745-6150</identifier><identifier>DOI: 10.1186/1745-6150-8-10</identifier><identifier>PMID: 23618224</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Analysis ; Binding sites ; Biology ; Brain research ; Breast Neoplasms - genetics ; Cancer ; Data mining ; Female ; Gene Expression Regulation, Neoplastic - genetics ; Gene Expression Regulation, Neoplastic - physiology ; Genes ; Genetic aspects ; Genomes ; Glioma - genetics ; Humans ; In Vitro Techniques ; Male ; Mammals ; MicroRNA ; MicroRNAs - genetics ; Neoplasms - genetics ; Ovarian Neoplasms - genetics ; Proteins ; Real-Time Polymerase Chain Reaction</subject><ispartof>Biology direct, 2013-04, Vol.8 (1), p.10-10, Article 10</ispartof><rights>COPYRIGHT 2013 BioMed Central Ltd.</rights><rights>2013 Laddha 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 Laddha et al.; licensee BioMed Central Ltd. 2013 Laddha et al.; licensee BioMed Central Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b643t-ff7faa90c4657438ace63e7785e52c52a552fd20a7ec1b3c1d6302eab8284163</citedby><cites>FETCH-LOGICAL-b643t-ff7faa90c4657438ace63e7785e52c52a552fd20a7ec1b3c1d6302eab8284163</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/PMC3680324/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3680324/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,27905,27906,53772,53774</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23618224$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Laddha, Saurabh V</creatorcontrib><creatorcontrib>Nayak, Subhashree</creatorcontrib><creatorcontrib>Paul, Deepanjan</creatorcontrib><creatorcontrib>Reddy, Rajasekhara</creatorcontrib><creatorcontrib>Sharma, Charu</creatorcontrib><creatorcontrib>Jha, Prerana</creatorcontrib><creatorcontrib>Hariharan, Manoj</creatorcontrib><creatorcontrib>Agrawal, Anurag</creatorcontrib><creatorcontrib>Chowdhury, Shantanu</creatorcontrib><creatorcontrib>Sarkar, Chitra</creatorcontrib><creatorcontrib>Mukhopadhyay, Arijit</creatorcontrib><title>Genome-wide analysis reveals downregulation of miR-379/miR-656 cluster in human cancers</title><title>Biology direct</title><addtitle>Biol Direct</addtitle><description>MicroRNAs (miRNAs) are non-uniformly distributed in genomes and ~30% of the miRNAs in the human genome are clustered. In this study we have focused on the imprinted miRNA cluster miR-379/miR-656 on 14q32.31 (hereafter C14) to test their coordinated function. We have analyzed expression profile of >1000 human miRNAs in >1400 samples representing seven different human tissue types obtained from cancer patients along with matched and unmatched controls.
We found 68% of the miRNAs in this cluster to be significantly downregulated in glioblastoma multiforme (GBM), 61% downregulated in kidney renal clear cell carcinoma (KIRC), 46% in breast invasive carcinoma (BRCA) and 14% in ovarian serous cystadenocarcinoma (OV). On a genome-wide scale C14 miRNAs accounted for 12-30% of the total downregulated miRNAs in different cancers. Pathway enrichment for the predicted targets of C14 miRNA was significant for cancer pathways, especially Glioma (p< 3.77x10⁻⁶, FDR<0.005). The observed downregulation was confirmed in GBM patients by real-time PCR, where 79% of C14 miRNAs (34/43) showed downregulation. In GBM samples, hypermethylation at C14 locus (p<0.003) and downregulation of MEF2, a crucial transcription factor for the cluster was observed which likely contribute to the observed downregulation of the entire miRNA cluster.
We provide compelling evidence that the entire C14 miRNA cluster is a tumor suppressor locus involved in multiple cancers, especially in GBM, and points toward a general mechanism of coordinated function for clustered miRNAs.</description><subject>Analysis</subject><subject>Binding sites</subject><subject>Biology</subject><subject>Brain research</subject><subject>Breast Neoplasms - genetics</subject><subject>Cancer</subject><subject>Data mining</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic - genetics</subject><subject>Gene Expression Regulation, Neoplastic - physiology</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genomes</subject><subject>Glioma - genetics</subject><subject>Humans</subject><subject>In Vitro Techniques</subject><subject>Male</subject><subject>Mammals</subject><subject>MicroRNA</subject><subject>MicroRNAs - genetics</subject><subject>Neoplasms - genetics</subject><subject>Ovarian Neoplasms - genetics</subject><subject>Proteins</subject><subject>Real-Time Polymerase Chain Reaction</subject><issn>1745-6150</issn><issn>1745-6150</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><sourceid>GNUQQ</sourceid><recordid>eNp1kk1LHTEUhofSUr-67bIEumkXo_lO7qZwEWsFoWAFlyGTOXONzCQ2mdH6782ovfW2lixOSJ48CW9OVb0neJ8QLQ-I4qKWROBa1wS_qrbXC6-fzbeqnZyvMOZcY_222qJMEk0p364ujiHEAepb3wKywfZ32WeU4AZsn1Ebb0OC1dTb0ceAYocGf1YztTiYqxQSuX7KIyTkA7qcBhuQs8FBynvVm64Y4N1T3a3Ovx6dH36rT78fnxwuT-tGcjbWXac6axfYcSkUZ9o6kAyU0gIEdYJaIWjXUmwVONIwR1rJMAXbaKo5kWy3-vKovZ6aAVoHYUy2N9fJDzbdmWi92dwJ_tKs4o1hUmNGeREsHwWNj_8RbO64OJg5VzPnarQhuDg-PT0ixZ8T5NEMPjvoexsgTtkQJpVWilFS0I9_oVdxSiX2B0rTkgFXf6iV7cH40MVytZulZikKoBYLRgu1_wJVRguDdzFA58v6xoHPGwcKM8KvcWWnnM3Jj7MX5S7FnBN060gINnPn_RvCh-c_scZ_txq7B8tq0TE</recordid><startdate>20130424</startdate><enddate>20130424</enddate><creator>Laddha, Saurabh V</creator><creator>Nayak, Subhashree</creator><creator>Paul, Deepanjan</creator><creator>Reddy, Rajasekhara</creator><creator>Sharma, Charu</creator><creator>Jha, Prerana</creator><creator>Hariharan, Manoj</creator><creator>Agrawal, Anurag</creator><creator>Chowdhury, Shantanu</creator><creator>Sarkar, Chitra</creator><creator>Mukhopadhyay, Arijit</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>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7SN</scope><scope>7SS</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PATMY</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PYCSY</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20130424</creationdate><title>Genome-wide analysis reveals downregulation of miR-379/miR-656 cluster in human cancers</title><author>Laddha, Saurabh V ; Nayak, Subhashree ; Paul, Deepanjan ; Reddy, Rajasekhara ; Sharma, Charu ; Jha, Prerana ; Hariharan, Manoj ; Agrawal, Anurag ; Chowdhury, Shantanu ; Sarkar, Chitra ; Mukhopadhyay, Arijit</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b643t-ff7faa90c4657438ace63e7785e52c52a552fd20a7ec1b3c1d6302eab8284163</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Analysis</topic><topic>Binding sites</topic><topic>Biology</topic><topic>Brain research</topic><topic>Breast Neoplasms - genetics</topic><topic>Cancer</topic><topic>Data mining</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic - genetics</topic><topic>Gene Expression Regulation, Neoplastic - physiology</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genomes</topic><topic>Glioma - genetics</topic><topic>Humans</topic><topic>In Vitro Techniques</topic><topic>Male</topic><topic>Mammals</topic><topic>MicroRNA</topic><topic>MicroRNAs - genetics</topic><topic>Neoplasms - genetics</topic><topic>Ovarian Neoplasms - genetics</topic><topic>Proteins</topic><topic>Real-Time Polymerase Chain Reaction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Laddha, Saurabh V</creatorcontrib><creatorcontrib>Nayak, Subhashree</creatorcontrib><creatorcontrib>Paul, Deepanjan</creatorcontrib><creatorcontrib>Reddy, Rajasekhara</creatorcontrib><creatorcontrib>Sharma, Charu</creatorcontrib><creatorcontrib>Jha, Prerana</creatorcontrib><creatorcontrib>Hariharan, Manoj</creatorcontrib><creatorcontrib>Agrawal, Anurag</creatorcontrib><creatorcontrib>Chowdhury, Shantanu</creatorcontrib><creatorcontrib>Sarkar, Chitra</creatorcontrib><creatorcontrib>Mukhopadhyay, Arijit</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: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest SciTech 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>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</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>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Environmental Science 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>Environmental Science Collection</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Biology direct</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Laddha, Saurabh V</au><au>Nayak, Subhashree</au><au>Paul, Deepanjan</au><au>Reddy, Rajasekhara</au><au>Sharma, Charu</au><au>Jha, Prerana</au><au>Hariharan, Manoj</au><au>Agrawal, Anurag</au><au>Chowdhury, Shantanu</au><au>Sarkar, Chitra</au><au>Mukhopadhyay, Arijit</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genome-wide analysis reveals downregulation of miR-379/miR-656 cluster in human cancers</atitle><jtitle>Biology direct</jtitle><addtitle>Biol Direct</addtitle><date>2013-04-24</date><risdate>2013</risdate><volume>8</volume><issue>1</issue><spage>10</spage><epage>10</epage><pages>10-10</pages><artnum>10</artnum><issn>1745-6150</issn><eissn>1745-6150</eissn><abstract>MicroRNAs (miRNAs) are non-uniformly distributed in genomes and ~30% of the miRNAs in the human genome are clustered. In this study we have focused on the imprinted miRNA cluster miR-379/miR-656 on 14q32.31 (hereafter C14) to test their coordinated function. We have analyzed expression profile of >1000 human miRNAs in >1400 samples representing seven different human tissue types obtained from cancer patients along with matched and unmatched controls.
We found 68% of the miRNAs in this cluster to be significantly downregulated in glioblastoma multiforme (GBM), 61% downregulated in kidney renal clear cell carcinoma (KIRC), 46% in breast invasive carcinoma (BRCA) and 14% in ovarian serous cystadenocarcinoma (OV). On a genome-wide scale C14 miRNAs accounted for 12-30% of the total downregulated miRNAs in different cancers. Pathway enrichment for the predicted targets of C14 miRNA was significant for cancer pathways, especially Glioma (p< 3.77x10⁻⁶, FDR<0.005). The observed downregulation was confirmed in GBM patients by real-time PCR, where 79% of C14 miRNAs (34/43) showed downregulation. In GBM samples, hypermethylation at C14 locus (p<0.003) and downregulation of MEF2, a crucial transcription factor for the cluster was observed which likely contribute to the observed downregulation of the entire miRNA cluster.
We provide compelling evidence that the entire C14 miRNA cluster is a tumor suppressor locus involved in multiple cancers, especially in GBM, and points toward a general mechanism of coordinated function for clustered miRNAs.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>23618224</pmid><doi>10.1186/1745-6150-8-10</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Analysis Binding sites Biology Brain research Breast Neoplasms - genetics Cancer Data mining Female Gene Expression Regulation, Neoplastic - genetics Gene Expression Regulation, Neoplastic - physiology Genes Genetic aspects Genomes Glioma - genetics Humans In Vitro Techniques Male Mammals MicroRNA MicroRNAs - genetics Neoplasms - genetics Ovarian Neoplasms - genetics Proteins Real-Time Polymerase Chain Reaction |
| title | Genome-wide analysis reveals downregulation of miR-379/miR-656 cluster in human cancers |
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