Antiproliferative effects of DNA methyltransferase 3B depletion are not associated with DNA demethylation
Silencing of genes by hypermethylation contributes to cancer progression and has been shown to occur with increased frequency at specific genomic loci. However, the precise mechanisms underlying the establishment and maintenance of aberrant methylation marks are still elusive. The de novo DNA methyl...
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| creator | Hagemann, Sabine Kuck, Dirk Stresemann, Carlo Prinz, Florian Brueckner, Bodo Mund, Cora Mumberg, Dominik Sommer, Anette |
| description | Silencing of genes by hypermethylation contributes to cancer progression and has been shown to occur with increased frequency at specific genomic loci. However, the precise mechanisms underlying the establishment and maintenance of aberrant methylation marks are still elusive. The de novo DNA methyltransferase 3B (DNMT3B) has been suggested to play an important role in the generation of cancer-specific methylation patterns. Previous studies have shown that a reduction of DNMT3B protein levels induces antiproliferative effects in cancer cells that were attributed to the demethylation and reactivation of tumor suppressor genes. However, methylation changes have not been analyzed in detail yet. Using RNA interference we reduced DNMT3B protein levels in colon cancer cell lines. Our results confirm that depletion of DNMT3B specifically reduced the proliferation rate of DNMT3B-overexpressing colon cancer cell lines. However, genome-scale DNA methylation profiling failed to reveal methylation changes at putative DNMT3B target genes, even in the complete absence of DNMT3B. These results show that DNMT3B is dispensable for the maintenance of aberrant DNA methylation patterns in human colon cancer cells and they have important implications for the development of targeted DNA methyltransferase inhibitors as epigenetic cancer drugs. |
| doi_str_mv | 10.1371/journal.pone.0036125 |
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However, the precise mechanisms underlying the establishment and maintenance of aberrant methylation marks are still elusive. The de novo DNA methyltransferase 3B (DNMT3B) has been suggested to play an important role in the generation of cancer-specific methylation patterns. Previous studies have shown that a reduction of DNMT3B protein levels induces antiproliferative effects in cancer cells that were attributed to the demethylation and reactivation of tumor suppressor genes. However, methylation changes have not been analyzed in detail yet. Using RNA interference we reduced DNMT3B protein levels in colon cancer cell lines. Our results confirm that depletion of DNMT3B specifically reduced the proliferation rate of DNMT3B-overexpressing colon cancer cell lines. However, genome-scale DNA methylation profiling failed to reveal methylation changes at putative DNMT3B target genes, even in the complete absence of DNMT3B. These results show that DNMT3B is dispensable for the maintenance of aberrant DNA methylation patterns in human colon cancer cells and they have important implications for the development of targeted DNA methyltransferase inhibitors as epigenetic cancer drugs.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0036125</identifier><identifier>PMID: 22563479</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aberration ; Activation ; Analysis ; Antiproliferatives ; Apoptosis ; Arrays ; Biology ; Biotechnology ; Caco-2 Cells ; Cancer ; Cancer research ; Cell Line ; Cell Line, Tumor ; Cell Proliferation ; Cell Survival - genetics ; Colon ; Colon cancer ; Colonic Neoplasms - genetics ; Colonic Neoplasms - metabolism ; Colonic Neoplasms - pathology ; Colorectal cancer ; Demethylation ; Deoxyribonucleic acid ; Depletion ; Development and progression ; DNA ; DNA (Cytosine-5-)-Methyltransferases - genetics ; DNA (Cytosine-5-)-Methyltransferases - metabolism ; DNA fingerprinting ; DNA Methylation ; DNA methyltransferase ; DNA Methyltransferase 3B ; Drug development ; Drugs ; Epigenetic inheritance ; Epigenetics ; Gene amplification ; Gene expression ; Gene Expression Regulation, Enzymologic ; Gene Expression Regulation, Neoplastic ; Gene silencing ; Genes ; Genetic aspects ; Genomes ; Genomics ; HCT116 Cells ; HT29 Cells ; Humans ; Immunoblotting ; Medical research ; Medicine ; Methylation ; Methyltransferases ; Neoplasms - genetics ; Neoplasms - metabolism ; Neoplasms - pathology ; Pharmaceuticals ; Proteins ; Reverse Transcriptase Polymerase Chain Reaction ; Ribonucleic acid ; RNA ; RNA Interference ; RNA-mediated interference ; Stress response ; Studies ; Tumor cell lines ; Tumor suppressor genes ; Tumors</subject><ispartof>PloS one, 2012-05, Vol.7 (5), p.e36125-e36125</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Hagemann 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. 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However, the precise mechanisms underlying the establishment and maintenance of aberrant methylation marks are still elusive. The de novo DNA methyltransferase 3B (DNMT3B) has been suggested to play an important role in the generation of cancer-specific methylation patterns. Previous studies have shown that a reduction of DNMT3B protein levels induces antiproliferative effects in cancer cells that were attributed to the demethylation and reactivation of tumor suppressor genes. However, methylation changes have not been analyzed in detail yet. Using RNA interference we reduced DNMT3B protein levels in colon cancer cell lines. Our results confirm that depletion of DNMT3B specifically reduced the proliferation rate of DNMT3B-overexpressing colon cancer cell lines. However, genome-scale DNA methylation profiling failed to reveal methylation changes at putative DNMT3B target genes, even in the complete absence of DNMT3B. These results show that DNMT3B is dispensable for the maintenance of aberrant DNA methylation patterns in human colon cancer cells and they have important implications for the development of targeted DNA methyltransferase inhibitors as epigenetic cancer drugs.</description><subject>Aberration</subject><subject>Activation</subject><subject>Analysis</subject><subject>Antiproliferatives</subject><subject>Apoptosis</subject><subject>Arrays</subject><subject>Biology</subject><subject>Biotechnology</subject><subject>Caco-2 Cells</subject><subject>Cancer</subject><subject>Cancer research</subject><subject>Cell Line</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation</subject><subject>Cell Survival - genetics</subject><subject>Colon</subject><subject>Colon cancer</subject><subject>Colonic Neoplasms - genetics</subject><subject>Colonic Neoplasms - metabolism</subject><subject>Colonic Neoplasms - pathology</subject><subject>Colorectal cancer</subject><subject>Demethylation</subject><subject>Deoxyribonucleic acid</subject><subject>Depletion</subject><subject>Development and progression</subject><subject>DNA</subject><subject>DNA (Cytosine-5-)-Methyltransferases - genetics</subject><subject>DNA (Cytosine-5-)-Methyltransferases - metabolism</subject><subject>DNA fingerprinting</subject><subject>DNA Methylation</subject><subject>DNA methyltransferase</subject><subject>DNA Methyltransferase 3B</subject><subject>Drug development</subject><subject>Drugs</subject><subject>Epigenetic inheritance</subject><subject>Epigenetics</subject><subject>Gene amplification</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Enzymologic</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Gene silencing</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genomes</subject><subject>Genomics</subject><subject>HCT116 Cells</subject><subject>HT29 Cells</subject><subject>Humans</subject><subject>Immunoblotting</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Methylation</subject><subject>Methyltransferases</subject><subject>Neoplasms - genetics</subject><subject>Neoplasms - metabolism</subject><subject>Neoplasms - pathology</subject><subject>Pharmaceuticals</subject><subject>Proteins</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA Interference</subject><subject>RNA-mediated interference</subject><subject>Stress response</subject><subject>Studies</subject><subject>Tumor cell lines</subject><subject>Tumor suppressor genes</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>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk9tuEzEQhi0EoiXwBghWQkJwkeDTHnKDFMopUkUlqLi1vN5x4shZp7a30LfHm2yrLOpF5Qtb9vf_Hs94EHpJ8IywknzYuM630s52roUZxqwgNH-ETsmc0WlBMXt8tD5Bz0LYYJyzqiieohNK84Lxcn6KzKKNZuedNRq8jOYaMtAaVAyZ09nnH4tsC3F9Y6OXbeiRABn7lDWwsxCNazPpIWtdzGQIThkZocn-mLjeSxs4iGVPPkdPtLQBXgzzBF1-_XJ59n16fvFtebY4n6qS5nGqNamqGqs5UE45qRgmuuRz1RQFBgwNLmpotMyp1JrV81Jy4JznWNP0KK3YBL0-2O6sC2JIUhCEUV5gRliViOWBaJzciJ03W-lvhJNG7DecXwnpo1EWRKVJkXwZo03R31JLojnWjACBhjR18vo43NbVW2gUtClRdmQ6PmnNWqzctWCME5aKMEHvBgPvrjoIUWxNUGCtbMF1KW5MccUJ5w9BCck5KZPxBL35D70_EQO1kumtptUuhah6U7HgZUkY5vsIZ_dQaaTqGpU-nzZpfyR4PxIkJsLfuJJdCGL56-fD2YvfY_btEbsGaeM6ONv1nyuMQX4AlXcheNB39SBY9L1zmw3R944YeifJXh3X8k502yzsH6nME14</recordid><startdate>20120501</startdate><enddate>20120501</enddate><creator>Hagemann, Sabine</creator><creator>Kuck, Dirk</creator><creator>Stresemann, Carlo</creator><creator>Prinz, Florian</creator><creator>Brueckner, Bodo</creator><creator>Mund, Cora</creator><creator>Mumberg, Dominik</creator><creator>Sommer, Anette</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>20120501</creationdate><title>Antiproliferative effects of DNA methyltransferase 3B depletion are not associated with DNA demethylation</title><author>Hagemann, Sabine ; Kuck, Dirk ; Stresemann, Carlo ; Prinz, Florian ; Brueckner, Bodo ; Mund, Cora ; Mumberg, Dominik ; Sommer, Anette</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c725t-ff188b0c9e242418301f749cd660e0ed06bedfa52aff3b97a4e44450f2225fc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Aberration</topic><topic>Activation</topic><topic>Analysis</topic><topic>Antiproliferatives</topic><topic>Apoptosis</topic><topic>Arrays</topic><topic>Biology</topic><topic>Biotechnology</topic><topic>Caco-2 Cells</topic><topic>Cancer</topic><topic>Cancer research</topic><topic>Cell Line</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation</topic><topic>Cell Survival - genetics</topic><topic>Colon</topic><topic>Colon cancer</topic><topic>Colonic Neoplasms - genetics</topic><topic>Colonic Neoplasms - metabolism</topic><topic>Colonic Neoplasms - pathology</topic><topic>Colorectal cancer</topic><topic>Demethylation</topic><topic>Deoxyribonucleic acid</topic><topic>Depletion</topic><topic>Development and progression</topic><topic>DNA</topic><topic>DNA (Cytosine-5-)-Methyltransferases - genetics</topic><topic>DNA (Cytosine-5-)-Methyltransferases - metabolism</topic><topic>DNA fingerprinting</topic><topic>DNA Methylation</topic><topic>DNA methyltransferase</topic><topic>DNA Methyltransferase 3B</topic><topic>Drug development</topic><topic>Drugs</topic><topic>Epigenetic inheritance</topic><topic>Epigenetics</topic><topic>Gene amplification</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Enzymologic</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Gene silencing</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genomes</topic><topic>Genomics</topic><topic>HCT116 Cells</topic><topic>HT29 Cells</topic><topic>Humans</topic><topic>Immunoblotting</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Methylation</topic><topic>Methyltransferases</topic><topic>Neoplasms - 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However, the precise mechanisms underlying the establishment and maintenance of aberrant methylation marks are still elusive. The de novo DNA methyltransferase 3B (DNMT3B) has been suggested to play an important role in the generation of cancer-specific methylation patterns. Previous studies have shown that a reduction of DNMT3B protein levels induces antiproliferative effects in cancer cells that were attributed to the demethylation and reactivation of tumor suppressor genes. However, methylation changes have not been analyzed in detail yet. Using RNA interference we reduced DNMT3B protein levels in colon cancer cell lines. Our results confirm that depletion of DNMT3B specifically reduced the proliferation rate of DNMT3B-overexpressing colon cancer cell lines. However, genome-scale DNA methylation profiling failed to reveal methylation changes at putative DNMT3B target genes, even in the complete absence of DNMT3B. These results show that DNMT3B is dispensable for the maintenance of aberrant DNA methylation patterns in human colon cancer cells and they have important implications for the development of targeted DNA methyltransferase inhibitors as epigenetic cancer drugs.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22563479</pmid><doi>10.1371/journal.pone.0036125</doi><tpages>e36125</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2012-05, Vol.7 (5), p.e36125-e36125 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1324603138 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Aberration Activation Analysis Antiproliferatives Apoptosis Arrays Biology Biotechnology Caco-2 Cells Cancer Cancer research Cell Line Cell Line, Tumor Cell Proliferation Cell Survival - genetics Colon Colon cancer Colonic Neoplasms - genetics Colonic Neoplasms - metabolism Colonic Neoplasms - pathology Colorectal cancer Demethylation Deoxyribonucleic acid Depletion Development and progression DNA DNA (Cytosine-5-)-Methyltransferases - genetics DNA (Cytosine-5-)-Methyltransferases - metabolism DNA fingerprinting DNA Methylation DNA methyltransferase DNA Methyltransferase 3B Drug development Drugs Epigenetic inheritance Epigenetics Gene amplification Gene expression Gene Expression Regulation, Enzymologic Gene Expression Regulation, Neoplastic Gene silencing Genes Genetic aspects Genomes Genomics HCT116 Cells HT29 Cells Humans Immunoblotting Medical research Medicine Methylation Methyltransferases Neoplasms - genetics Neoplasms - metabolism Neoplasms - pathology Pharmaceuticals Proteins Reverse Transcriptase Polymerase Chain Reaction Ribonucleic acid RNA RNA Interference RNA-mediated interference Stress response Studies Tumor cell lines Tumor suppressor genes Tumors |
| title | Antiproliferative effects of DNA methyltransferase 3B depletion are not associated with DNA demethylation |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-02T09%3A59%3A15IST&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=Antiproliferative%20effects%20of%20DNA%20methyltransferase%203B%20depletion%20are%20not%20associated%20with%20DNA%20demethylation&rft.jtitle=PloS%20one&rft.au=Hagemann,%20Sabine&rft.date=2012-05-01&rft.volume=7&rft.issue=5&rft.spage=e36125&rft.epage=e36125&rft.pages=e36125-e36125&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0036125&rft_dat=%3Cgale_plos_%3EA477130456%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=1324603138&rft_id=info:pmid/22563479&rft_galeid=A477130456&rft_doaj_id=oai_doaj_org_article_8f16222332d64445ba1f40f31e1ed1db&rfr_iscdi=true |