{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T04:46:40Z","timestamp":1777006000838,"version":"3.51.4"},"reference-count":51,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2011,12,27]],"date-time":"2011-12-27T00:00:00Z","timestamp":1324944000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Carcinogenesis is a multistep sequential process of clonal expansion of initiated cells associated with the accumulation of multiple cancer\u2010specific heritable phenotypes. The acquisition of these heritable cancer\u2010specific alterations may be triggered by mutational and\/or non\u2010mutational changes in the genome that affect the regulation of gene expression. Currently, cancer\u2010specific epigenetically mediated changes in gene expression are regarded as driving events in tumorigenesis. In the present study, we investigated the role of gene\u2010specific expression changes in the mechanism of rat hepatocarcinogenesis induced by the complete hepatocarcinogen 2\u2010acetylaminofluorene (2\u2010AAF). The results of the present study demonstrate significant alterations in gene expression, especially of <jats:italic>Mat1a<\/jats:italic> and <jats:italic>Mthfr<\/jats:italic> genes, during early stages of rat 2\u2010AAF\u2010induced liver carcinogenesis. Both of these genes were downregulated in the livers of 2\u2010AAF\u2010treated male rats. Inhibition of <jats:italic>Mat1a<\/jats:italic> expression was associated with an increase in histone H3 lysine 27 trimethylation and a decrease in histone H3 lysine 18 acetylation at the gene promoter\/first exon region. Additionally, we demonstrate for the first time a critical contribution of miR\u201022 and miR\u201029b microRNAs in the inhibition of <jats:italic>Mat1a<\/jats:italic> and <jats:italic>Mthfr<\/jats:italic> gene expression during 2\u2010AAF\u2010induced rat hepatocarcinogenesis. The downregulation of <jats:italic>Mat1a<\/jats:italic> and <jats:italic>Mthfr<\/jats:italic> genes was accompanied by marked functional alterations in one\u2010carbon metabolism. The results of the present study suggest that downregulation of the <jats:italic>Mat1a<\/jats:italic> and <jats:italic>Mthfr<\/jats:italic> genes may be one of the main driver events that promote liver carcinogenesis by causing a profound accumulation of subsequent epigenetic abnormalities during progression of the carcinogenic process. \u00a9 2011 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/mc.21861","type":"journal-article","created":{"date-parts":[[2011,12,27]],"date-time":"2011-12-27T13:40:01Z","timestamp":1324993201000},"page":"318-327","source":"Crossref","is-referenced-by-count":41,"title":["Role of epigenetic and miR\u201022 and miR\u201029b alterations in the downregulation of <i>Mat1a<\/i> and <i>Mthfr<\/i> genes in early preneoplastic livers in rats induced by 2\u2010acetylaminofluorene"],"prefix":"10.1002","volume":"52","author":[{"given":"Igor","family":"Koturbash","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stepan","family":"Melnyk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. Jill","family":"James","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frederick A.","family":"Beland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Igor P.","family":"Pogribny","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2011,12,27]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.10320"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1087"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgm303"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.24492"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-2852"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.01.029"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2010.10.005"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.02.013"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2009.01434.x"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra023075"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1535-6108(02)00061-2"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205598"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1535-6108(02)00234-9"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0905767106"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.159"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp251"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.2217\/epi.10.9"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexmp.2010.01.005"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-380866-0.60010-1"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/55.1.44"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.73"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2350-11-77"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/22.15.2990"},{"key":"e_1_2_6_25_2","doi-asserted-by":"crossref","first-page":"126","DOI":"10.2144\/96211rr04","article-title":"Cytosine methylation: Quantitation by automated genomic sequencing and GENESCAN analysis","volume":"21","author":"Paul CL","year":"1996","journal-title":"Biotechniques"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/7.5.689"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2008.12.021"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2004.11.024"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-10-317"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203898"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3835(96)04509-0"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0501-29"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/em.20342"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1076997"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0707292104"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1155544"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09267"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.2217\/pgs.10.26"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0021851"},{"key":"e_1_2_6_40_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1010978107"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510290525"},{"key":"e_1_2_6_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(01)00590-1"},{"key":"e_1_2_6_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(00)80122-1"},{"key":"e_1_2_6_44_2","doi-asserted-by":"publisher","DOI":"10.3181\/0901-MR-40"},{"key":"e_1_2_6_45_2","doi-asserted-by":"publisher","DOI":"10.3816\/CCC.2006.n.004"},{"key":"e_1_2_6_46_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-2489"},{"key":"e_1_2_6_47_2","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.14.1.95"},{"key":"e_1_2_6_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1357-2725(99)00140-5"},{"key":"e_1_2_6_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.154"},{"key":"e_1_2_6_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(00)01551-6"},{"key":"e_1_2_6_51_2","article-title":"A DNA methylation fingerprint of 1628 human samples","author":"Fernandez AF","year":"2011","journal-title":"Genome Res"},{"key":"e_1_2_6_52_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.22940"}],"container-title":["Molecular Carcinogenesis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmc.21861","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmc.21861","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mc.21861","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T10:18:58Z","timestamp":1697624338000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mc.21861"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,12,27]]},"references-count":51,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2013,4]]}},"alternative-id":["10.1002\/mc.21861"],"URL":"https:\/\/doi.org\/10.1002\/mc.21861","archive":["Portico"],"relation":{},"ISSN":["0899-1987","1098-2744"],"issn-type":[{"value":"0899-1987","type":"print"},{"value":"1098-2744","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,12,27]]}}}