Expression of DNMT1 and DNMT3a are regulated by GLI1 in human pancreatic cancer
GLI1, as an indispensable transcriptional factor of Hedgehog signaling pathway, plays an important role in the development of pancreatic cancer (PC). DNA methyltransferases (DNMTs) mediate the methylation of quantity of tumor-related genes. Our study aimed to explore the relationship between GLI1 an...
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| Veröffentlicht in: | PloS one 2011-11, Vol.6 (11), p.e27684 |
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| creator | He, ShanShan Wang, Feng Yang, LiJuan Guo, ChuanYong Wan, Rong Ke, AiWu Xu, Ling Hu, GuoYong Xu, XuanFu Shen, Jie Wang, XingPeng |
| description | GLI1, as an indispensable transcriptional factor of Hedgehog signaling pathway, plays an important role in the development of pancreatic cancer (PC). DNA methyltransferases (DNMTs) mediate the methylation of quantity of tumor-related genes. Our study aimed to explore the relationship between GLI1 and DNMTs.
Expressions of GLI1 and DNMTs were detected in tumor and adjacent normal tissues of PC patients by immunohistochemistry (IHC). PANC-1 cells were treated by cyclopamine and GLI1-siRNA, while BxPC-3 cells were transfected with overexpression-GLI1 lentiviral vector. Then GLI1 and DNMTs expression were analyzed by qRT-PCR and western blot (WB). Then we took chromatin immunoprecipitation (ChIP) to demonstrate GLI1 bind to DNMT1. Finally, nested MSP was taken to valuate the methylation levels of APC and hMLH1, when GLI1 expression altered.
IHC result suggested the expressions of GLI1, DNMT1 and DNMT3a in PC tissues were all higher than those in adjacent normal tissues (p |
| doi_str_mv | 10.1371/journal.pone.0027684 |
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Expressions of GLI1 and DNMTs were detected in tumor and adjacent normal tissues of PC patients by immunohistochemistry (IHC). PANC-1 cells were treated by cyclopamine and GLI1-siRNA, while BxPC-3 cells were transfected with overexpression-GLI1 lentiviral vector. Then GLI1 and DNMTs expression were analyzed by qRT-PCR and western blot (WB). Then we took chromatin immunoprecipitation (ChIP) to demonstrate GLI1 bind to DNMT1. Finally, nested MSP was taken to valuate the methylation levels of APC and hMLH1, when GLI1 expression altered.
IHC result suggested the expressions of GLI1, DNMT1 and DNMT3a in PC tissues were all higher than those in adjacent normal tissues (p<0.05). After GLI1 expression repressed by cyclopamine in mRNA and protein level (down-regulation 88.1±2.2%, 86.4±2.2%, respectively), DNMT1 and DNMT3a mRNA and protein level decreased by 91.6%±2.2% and 83.8±4.8%, 87.4±2.7% and 84.4±1.3%, respectively. When further knocked down the expression of GLI1 by siRNA (mRNA decreased by 88.6±2.1%, protein decreased by 63.5±4.5%), DNMT1 and DNMT3a mRNA decreased by 80.9±2.3% and 78.6±3.8% and protein decreased by 64.8±2.8% and 67.5±5.6%, respectively. Over-expression of GLI1 by GLI1 gene transfection (mRNA increased by 655.5±85.9%, and protein increased by 272.3±14.4%.), DNMT1 and DNMT3a mRNA and protein increased by 293.0±14.8% and 578.3±58.5%, 143.5±17.4% and 214.0±18.9%, respectively. ChIP assays showed GLI1 protein bound to DNMT1 but not to DNMT3a. Results of nested MSP demonstrated GLI1 expression affected the DNA methylation level of APC but not hMLH1 in PC.
DNMT1 and DNMT3a are regulated by GLI1 in PC, and DNMT1 is its direct target gene.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0027684</identifier><identifier>PMID: 22110720</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adenomatous polyposis coli ; Adenomatous Polyposis Coli - genetics ; Adenomatous Polyposis Coli - metabolism ; Adenomatous Polyposis Coli - pathology ; Biology ; Cancer ; Cell cycle ; Cell Line, Tumor ; Chromatin ; Colorectal cancer ; Deoxyribonucleic acid ; DNA ; DNA (Cytosine-5-)-Methyltransferase 1 ; DNA (Cytosine-5-)-Methyltransferases - genetics ; DNA (Cytosine-5-)-Methyltransferases - metabolism ; DNA methylation ; DNA Methylation - drug effects ; DNA Methylation - genetics ; DNMT1 protein ; Ethics ; Gastroenterology ; Gene expression ; Gene Expression Regulation, Neoplastic - drug effects ; Gene Expression Regulation, Neoplastic - genetics ; Genes ; GLI1 gene ; Gli1 protein ; Hedgehog protein ; Hepatitis ; Hospitals ; Humans ; Immunohistochemistry ; Immunoprecipitation ; Leukemia ; Ligands ; Liver cancer ; Lung cancer ; Medical prognosis ; Medicine ; Metastasis ; Methylation ; Methyltransferases ; MicroRNAs ; Oncogene Proteins - deficiency ; Oncogene Proteins - genetics ; Oncogene Proteins - metabolism ; Overexpression ; Pancreatic cancer ; Pancreatic Neoplasms - genetics ; Pancreatic Neoplasms - metabolism ; Pancreatic Neoplasms - pathology ; Promoter Regions, Genetic - drug effects ; Promoter Regions, Genetic - genetics ; Protein binding ; RNA ; RNA, Small Interfering - genetics ; Signal transduction ; Signaling ; siRNA ; Tissues ; Trans-Activators - deficiency ; Trans-Activators - genetics ; Trans-Activators - metabolism ; Transfection ; Up-Regulation - drug effects ; Up-Regulation - genetics ; Veratrum Alkaloids - pharmacology ; Zinc Finger Protein GLI1</subject><ispartof>PloS one, 2011-11, Vol.6 (11), p.e27684</ispartof><rights>COPYRIGHT 2011 Public Library of Science</rights><rights>2011 He 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>He et al. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c757t-41fc9a4e0294a720a5dab828df492a4fafc9765b691cca1b4bb76d6db9209fe33</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3215738/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3215738/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,2096,2915,23847,27905,27906,53772,53774,79349,79350</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22110720$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Guan, Xin-yuan</contributor><creatorcontrib>He, ShanShan</creatorcontrib><creatorcontrib>Wang, Feng</creatorcontrib><creatorcontrib>Yang, LiJuan</creatorcontrib><creatorcontrib>Guo, ChuanYong</creatorcontrib><creatorcontrib>Wan, Rong</creatorcontrib><creatorcontrib>Ke, AiWu</creatorcontrib><creatorcontrib>Xu, Ling</creatorcontrib><creatorcontrib>Hu, GuoYong</creatorcontrib><creatorcontrib>Xu, XuanFu</creatorcontrib><creatorcontrib>Shen, Jie</creatorcontrib><creatorcontrib>Wang, XingPeng</creatorcontrib><title>Expression of DNMT1 and DNMT3a are regulated by GLI1 in human pancreatic cancer</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>GLI1, as an indispensable transcriptional factor of Hedgehog signaling pathway, plays an important role in the development of pancreatic cancer (PC). DNA methyltransferases (DNMTs) mediate the methylation of quantity of tumor-related genes. Our study aimed to explore the relationship between GLI1 and DNMTs.
Expressions of GLI1 and DNMTs were detected in tumor and adjacent normal tissues of PC patients by immunohistochemistry (IHC). PANC-1 cells were treated by cyclopamine and GLI1-siRNA, while BxPC-3 cells were transfected with overexpression-GLI1 lentiviral vector. Then GLI1 and DNMTs expression were analyzed by qRT-PCR and western blot (WB). Then we took chromatin immunoprecipitation (ChIP) to demonstrate GLI1 bind to DNMT1. Finally, nested MSP was taken to valuate the methylation levels of APC and hMLH1, when GLI1 expression altered.
IHC result suggested the expressions of GLI1, DNMT1 and DNMT3a in PC tissues were all higher than those in adjacent normal tissues (p<0.05). After GLI1 expression repressed by cyclopamine in mRNA and protein level (down-regulation 88.1±2.2%, 86.4±2.2%, respectively), DNMT1 and DNMT3a mRNA and protein level decreased by 91.6%±2.2% and 83.8±4.8%, 87.4±2.7% and 84.4±1.3%, respectively. When further knocked down the expression of GLI1 by siRNA (mRNA decreased by 88.6±2.1%, protein decreased by 63.5±4.5%), DNMT1 and DNMT3a mRNA decreased by 80.9±2.3% and 78.6±3.8% and protein decreased by 64.8±2.8% and 67.5±5.6%, respectively. Over-expression of GLI1 by GLI1 gene transfection (mRNA increased by 655.5±85.9%, and protein increased by 272.3±14.4%.), DNMT1 and DNMT3a mRNA and protein increased by 293.0±14.8% and 578.3±58.5%, 143.5±17.4% and 214.0±18.9%, respectively. ChIP assays showed GLI1 protein bound to DNMT1 but not to DNMT3a. Results of nested MSP demonstrated GLI1 expression affected the DNA methylation level of APC but not hMLH1 in PC.
DNMT1 and DNMT3a are regulated by GLI1 in PC, and DNMT1 is its direct target gene.</description><subject>Adenomatous polyposis coli</subject><subject>Adenomatous Polyposis Coli - genetics</subject><subject>Adenomatous Polyposis Coli - metabolism</subject><subject>Adenomatous Polyposis Coli - pathology</subject><subject>Biology</subject><subject>Cancer</subject><subject>Cell cycle</subject><subject>Cell Line, Tumor</subject><subject>Chromatin</subject><subject>Colorectal cancer</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA (Cytosine-5-)-Methyltransferase 1</subject><subject>DNA (Cytosine-5-)-Methyltransferases - genetics</subject><subject>DNA (Cytosine-5-)-Methyltransferases - metabolism</subject><subject>DNA methylation</subject><subject>DNA Methylation - drug effects</subject><subject>DNA Methylation - genetics</subject><subject>DNMT1 protein</subject><subject>Ethics</subject><subject>Gastroenterology</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Gene Expression Regulation, Neoplastic - genetics</subject><subject>Genes</subject><subject>GLI1 gene</subject><subject>Gli1 protein</subject><subject>Hedgehog protein</subject><subject>Hepatitis</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Immunoprecipitation</subject><subject>Leukemia</subject><subject>Ligands</subject><subject>Liver cancer</subject><subject>Lung cancer</subject><subject>Medical prognosis</subject><subject>Medicine</subject><subject>Metastasis</subject><subject>Methylation</subject><subject>Methyltransferases</subject><subject>MicroRNAs</subject><subject>Oncogene Proteins - deficiency</subject><subject>Oncogene Proteins - genetics</subject><subject>Oncogene Proteins - metabolism</subject><subject>Overexpression</subject><subject>Pancreatic cancer</subject><subject>Pancreatic Neoplasms - genetics</subject><subject>Pancreatic Neoplasms - metabolism</subject><subject>Pancreatic Neoplasms - pathology</subject><subject>Promoter Regions, Genetic - drug effects</subject><subject>Promoter Regions, Genetic - genetics</subject><subject>Protein binding</subject><subject>RNA</subject><subject>RNA, Small Interfering - genetics</subject><subject>Signal transduction</subject><subject>Signaling</subject><subject>siRNA</subject><subject>Tissues</subject><subject>Trans-Activators - deficiency</subject><subject>Trans-Activators - genetics</subject><subject>Trans-Activators - metabolism</subject><subject>Transfection</subject><subject>Up-Regulation - drug effects</subject><subject>Up-Regulation - genetics</subject><subject>Veratrum Alkaloids - pharmacology</subject><subject>Zinc Finger Protein GLI1</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</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><sourceid>DOA</sourceid><recordid>eNqNkttrFDEUxgdR7EX_A9GAIPiwa25zyYtQaq0LqwtafQ1ncpmdZWYyJjPS_vdNu9OyAwqShxyS3_nycfIlySuCl4Tl5MPOjb6DZtm7ziwxpnlW8CfJMRGMLjKK2dOD-ig5CWGHccqKLHueHFFKCM4pPk42F9e9NyHUrkPOok_fvl4RBJ2-rxgg8AZ5U40NDEaj8gZdrlcE1R3aji10qIdOeQNDrZCKpfEvkmcWmmBeTvtp8vPzxdX5l8V6c7k6P1svVJ7mw4ITqwRwg6ngEI1AqqEsaKEtFxS4hXidZ2mZCaIUkJKXZZ7pTJeCYmENY6fJm71u37ggp1kESRihJI1QHonVntAOdrL3dQv-Rjqo5f2B85UEH403RoqCaco116pIudAgbK6pJUVRlpZxMFHr4_TaWLZGK9MNHpqZ6Pymq7eycn8ki25yVkSBt5OAd79HE4Z_WJ6oCqKrurMuiqm2Dkqe8fi_GcNMRGr5FyoubdpaxTTYOp7PGt7PGiIzmOuhgjEEufrx_f_Zza85--6A3Rpohm1wzTjEMIU5yPeg8i4Eb-zj5AiWd2F-mIa8C7OcwhzbXh9O_bHpIb3sFluM7Yk</recordid><startdate>20111114</startdate><enddate>20111114</enddate><creator>He, ShanShan</creator><creator>Wang, Feng</creator><creator>Yang, LiJuan</creator><creator>Guo, ChuanYong</creator><creator>Wan, Rong</creator><creator>Ke, AiWu</creator><creator>Xu, Ling</creator><creator>Hu, GuoYong</creator><creator>Xu, XuanFu</creator><creator>Shen, Jie</creator><creator>Wang, XingPeng</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>5PM</scope><scope>DOA</scope></search><sort><creationdate>20111114</creationdate><title>Expression of DNMT1 and DNMT3a are regulated by GLI1 in human pancreatic cancer</title><author>He, ShanShan ; Wang, Feng ; Yang, LiJuan ; Guo, ChuanYong ; Wan, Rong ; Ke, AiWu ; Xu, Ling ; Hu, GuoYong ; Xu, XuanFu ; Shen, Jie ; Wang, XingPeng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c757t-41fc9a4e0294a720a5dab828df492a4fafc9765b691cca1b4bb76d6db9209fe33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adenomatous polyposis coli</topic><topic>Adenomatous Polyposis Coli - genetics</topic><topic>Adenomatous Polyposis Coli - metabolism</topic><topic>Adenomatous Polyposis Coli - pathology</topic><topic>Biology</topic><topic>Cancer</topic><topic>Cell cycle</topic><topic>Cell Line, Tumor</topic><topic>Chromatin</topic><topic>Colorectal cancer</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA (Cytosine-5-)-Methyltransferase 1</topic><topic>DNA (Cytosine-5-)-Methyltransferases - genetics</topic><topic>DNA (Cytosine-5-)-Methyltransferases - metabolism</topic><topic>DNA methylation</topic><topic>DNA Methylation - drug effects</topic><topic>DNA Methylation - genetics</topic><topic>DNMT1 protein</topic><topic>Ethics</topic><topic>Gastroenterology</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Neoplastic - drug effects</topic><topic>Gene Expression Regulation, Neoplastic - genetics</topic><topic>Genes</topic><topic>GLI1 gene</topic><topic>Gli1 protein</topic><topic>Hedgehog protein</topic><topic>Hepatitis</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Immunoprecipitation</topic><topic>Leukemia</topic><topic>Ligands</topic><topic>Liver cancer</topic><topic>Lung cancer</topic><topic>Medical prognosis</topic><topic>Medicine</topic><topic>Metastasis</topic><topic>Methylation</topic><topic>Methyltransferases</topic><topic>MicroRNAs</topic><topic>Oncogene Proteins - deficiency</topic><topic>Oncogene Proteins - genetics</topic><topic>Oncogene Proteins - metabolism</topic><topic>Overexpression</topic><topic>Pancreatic cancer</topic><topic>Pancreatic Neoplasms - genetics</topic><topic>Pancreatic Neoplasms - metabolism</topic><topic>Pancreatic Neoplasms - pathology</topic><topic>Promoter Regions, Genetic - drug effects</topic><topic>Promoter Regions, Genetic - genetics</topic><topic>Protein binding</topic><topic>RNA</topic><topic>RNA, Small Interfering - genetics</topic><topic>Signal transduction</topic><topic>Signaling</topic><topic>siRNA</topic><topic>Tissues</topic><topic>Trans-Activators - deficiency</topic><topic>Trans-Activators - genetics</topic><topic>Trans-Activators - metabolism</topic><topic>Transfection</topic><topic>Up-Regulation - drug effects</topic><topic>Up-Regulation - genetics</topic><topic>Veratrum Alkaloids - pharmacology</topic><topic>Zinc Finger Protein GLI1</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>He, ShanShan</creatorcontrib><creatorcontrib>Wang, Feng</creatorcontrib><creatorcontrib>Yang, LiJuan</creatorcontrib><creatorcontrib>Guo, ChuanYong</creatorcontrib><creatorcontrib>Wan, Rong</creatorcontrib><creatorcontrib>Ke, AiWu</creatorcontrib><creatorcontrib>Xu, Ling</creatorcontrib><creatorcontrib>Hu, GuoYong</creatorcontrib><creatorcontrib>Xu, XuanFu</creatorcontrib><creatorcontrib>Shen, Jie</creatorcontrib><creatorcontrib>Wang, XingPeng</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>ProQuest 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>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>He, ShanShan</au><au>Wang, Feng</au><au>Yang, LiJuan</au><au>Guo, ChuanYong</au><au>Wan, Rong</au><au>Ke, AiWu</au><au>Xu, Ling</au><au>Hu, GuoYong</au><au>Xu, XuanFu</au><au>Shen, Jie</au><au>Wang, XingPeng</au><au>Guan, Xin-yuan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression of DNMT1 and DNMT3a are regulated by GLI1 in human pancreatic cancer</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2011-11-14</date><risdate>2011</risdate><volume>6</volume><issue>11</issue><spage>e27684</spage><pages>e27684-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>GLI1, as an indispensable transcriptional factor of Hedgehog signaling pathway, plays an important role in the development of pancreatic cancer (PC). DNA methyltransferases (DNMTs) mediate the methylation of quantity of tumor-related genes. Our study aimed to explore the relationship between GLI1 and DNMTs.
Expressions of GLI1 and DNMTs were detected in tumor and adjacent normal tissues of PC patients by immunohistochemistry (IHC). PANC-1 cells were treated by cyclopamine and GLI1-siRNA, while BxPC-3 cells were transfected with overexpression-GLI1 lentiviral vector. Then GLI1 and DNMTs expression were analyzed by qRT-PCR and western blot (WB). Then we took chromatin immunoprecipitation (ChIP) to demonstrate GLI1 bind to DNMT1. Finally, nested MSP was taken to valuate the methylation levels of APC and hMLH1, when GLI1 expression altered.
IHC result suggested the expressions of GLI1, DNMT1 and DNMT3a in PC tissues were all higher than those in adjacent normal tissues (p<0.05). After GLI1 expression repressed by cyclopamine in mRNA and protein level (down-regulation 88.1±2.2%, 86.4±2.2%, respectively), DNMT1 and DNMT3a mRNA and protein level decreased by 91.6%±2.2% and 83.8±4.8%, 87.4±2.7% and 84.4±1.3%, respectively. When further knocked down the expression of GLI1 by siRNA (mRNA decreased by 88.6±2.1%, protein decreased by 63.5±4.5%), DNMT1 and DNMT3a mRNA decreased by 80.9±2.3% and 78.6±3.8% and protein decreased by 64.8±2.8% and 67.5±5.6%, respectively. Over-expression of GLI1 by GLI1 gene transfection (mRNA increased by 655.5±85.9%, and protein increased by 272.3±14.4%.), DNMT1 and DNMT3a mRNA and protein increased by 293.0±14.8% and 578.3±58.5%, 143.5±17.4% and 214.0±18.9%, respectively. ChIP assays showed GLI1 protein bound to DNMT1 but not to DNMT3a. Results of nested MSP demonstrated GLI1 expression affected the DNA methylation level of APC but not hMLH1 in PC.
DNMT1 and DNMT3a are regulated by GLI1 in PC, and DNMT1 is its direct target gene.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22110720</pmid><doi>10.1371/journal.pone.0027684</doi><tpages>e27684</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2011-11, Vol.6 (11), p.e27684 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1312159207 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adenomatous polyposis coli Adenomatous Polyposis Coli - genetics Adenomatous Polyposis Coli - metabolism Adenomatous Polyposis Coli - pathology Biology Cancer Cell cycle Cell Line, Tumor Chromatin Colorectal cancer Deoxyribonucleic acid DNA DNA (Cytosine-5-)-Methyltransferase 1 DNA (Cytosine-5-)-Methyltransferases - genetics DNA (Cytosine-5-)-Methyltransferases - metabolism DNA methylation DNA Methylation - drug effects DNA Methylation - genetics DNMT1 protein Ethics Gastroenterology Gene expression Gene Expression Regulation, Neoplastic - drug effects Gene Expression Regulation, Neoplastic - genetics Genes GLI1 gene Gli1 protein Hedgehog protein Hepatitis Hospitals Humans Immunohistochemistry Immunoprecipitation Leukemia Ligands Liver cancer Lung cancer Medical prognosis Medicine Metastasis Methylation Methyltransferases MicroRNAs Oncogene Proteins - deficiency Oncogene Proteins - genetics Oncogene Proteins - metabolism Overexpression Pancreatic cancer Pancreatic Neoplasms - genetics Pancreatic Neoplasms - metabolism Pancreatic Neoplasms - pathology Promoter Regions, Genetic - drug effects Promoter Regions, Genetic - genetics Protein binding RNA RNA, Small Interfering - genetics Signal transduction Signaling siRNA Tissues Trans-Activators - deficiency Trans-Activators - genetics Trans-Activators - metabolism Transfection Up-Regulation - drug effects Up-Regulation - genetics Veratrum Alkaloids - pharmacology Zinc Finger Protein GLI1 |
| title | Expression of DNMT1 and DNMT3a are regulated by GLI1 in human pancreatic cancer |
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