{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:33:51Z","timestamp":1760150031452,"version":"build-2065373602"},"reference-count":53,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,10,14]],"date-time":"2023-10-14T00:00:00Z","timestamp":1697241600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Programa Operacional Competitividade e Internacionaliza\u00e7\u00e3o (POCI)","award":["PTDC\/MECONC\/29030\/2017","NORTE 2020","CEEC\/1048\/2019","CEEC-IND\/00371\/2017","RNCCCP.CCC-CI-IPOP-LAB3"],"award-info":[{"award-number":["PTDC\/MECONC\/29030\/2017","NORTE 2020","CEEC\/1048\/2019","CEEC-IND\/00371\/2017","RNCCCP.CCC-CI-IPOP-LAB3"]}]},{"DOI":"10.13039\/501100001871","name":"national funds (OE) through FCT\/MCTES, in the scope of the project HyTherCaP","doi-asserted-by":"publisher","award":["PTDC\/MECONC\/29030\/2017","NORTE 2020","CEEC\/1048\/2019","CEEC-IND\/00371\/2017","RNCCCP.CCC-CI-IPOP-LAB3"],"award-info":[{"award-number":["PTDC\/MECONC\/29030\/2017","NORTE 2020","CEEC\/1048\/2019","CEEC-IND\/00371\/2017","RNCCCP.CCC-CI-IPOP-LAB3"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Norte Portugal Regional Operacional Program","award":["PTDC\/MECONC\/29030\/2017","NORTE 2020","CEEC\/1048\/2019","CEEC-IND\/00371\/2017","RNCCCP.CCC-CI-IPOP-LAB3"],"award-info":[{"award-number":["PTDC\/MECONC\/29030\/2017","NORTE 2020","CEEC\/1048\/2019","CEEC-IND\/00371\/2017","RNCCCP.CCC-CI-IPOP-LAB3"]}]},{"DOI":"10.13039\/501100001871","name":"Portuguese Foundation for Science and Technology (FCT)","doi-asserted-by":"publisher","award":["PTDC\/MECONC\/29030\/2017","NORTE 2020","CEEC\/1048\/2019","CEEC-IND\/00371\/2017","RNCCCP.CCC-CI-IPOP-LAB3"],"award-info":[{"award-number":["PTDC\/MECONC\/29030\/2017","NORTE 2020","CEEC\/1048\/2019","CEEC-IND\/00371\/2017","RNCCCP.CCC-CI-IPOP-LAB3"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Porto Comprehensive Cancer Center","award":["PTDC\/MECONC\/29030\/2017","NORTE 2020","CEEC\/1048\/2019","CEEC-IND\/00371\/2017","RNCCCP.CCC-CI-IPOP-LAB3"],"award-info":[{"award-number":["PTDC\/MECONC\/29030\/2017","NORTE 2020","CEEC\/1048\/2019","CEEC-IND\/00371\/2017","RNCCCP.CCC-CI-IPOP-LAB3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The androgens\/androgen receptor (AR) axis is the main therapeutic target in prostate cancer (PCa). However, while initially responsive, a subset of tumors loses AR expression through mechanisms putatively associated with epigenetic modifications. In this study, we assessed the link between the presence of CpG methylation in the 5\u2032UTR and promoter regions of AR and loss of AR expression. Hence, we characterized and compared the methylation signature at CpG resolution of these regulatory regions in vitro, both at basal levels and following treatment with 5-aza-2-deoxycytidine (DAC) alone, or in combination with Trichostatin A (TSA). Our results showed heterogeneity in the methylation signature of AR negative cell lines and pinpointed the proximal promoter region as the most consistently methylated site in DU-145. Furthermore, this region was extremely resistant to the demethylating effects of DAC and was only significantly demethylated upon concomitant treatment with TSA. Nevertheless, no AR re-expression was detected at the mRNA or protein level. Importantly, after treatment, there was a significant increase in repressive histone marks at AR region 1 in DU-145 cells. Altogether, our data indicate that AR region 1 genomic availability is crucial for AR expression and that the inhibition of histone methyltransferases might hold promise for AR re-expression.<\/jats:p>","DOI":"10.3390\/biom13101526","type":"journal-article","created":{"date-parts":[[2023,10,14]],"date-time":"2023-10-14T14:38:42Z","timestamp":1697294322000},"page":"1526","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Novel Insights on the Role of Epigenetics in Androgen Receptor\u2019s Expression in Prostate Cancer"],"prefix":"10.3390","volume":"13","author":[{"given":"V\u00e2nia","family":"Camilo","sequence":"first","affiliation":[{"name":"Cancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP)\/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Center (Porto.CCC) Raquel Seruca, R. Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"given":"Mariana Br\u00fctt","family":"Pacheco","sequence":"additional","affiliation":[{"name":"Cancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP)\/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Center (Porto.CCC) Raquel Seruca, R. Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7272-7300","authenticated-orcid":false,"given":"Filipa","family":"Moreira-Silva","sequence":"additional","affiliation":[{"name":"Cancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP)\/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Center (Porto.CCC) Raquel Seruca, R. Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"given":"Gon\u00e7alo","family":"Outeiro-Pinho","sequence":"additional","affiliation":[{"name":"Cancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP)\/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Center (Porto.CCC) Raquel Seruca, R. Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0372-2493","authenticated-orcid":false,"given":"V\u00edtor M.","family":"Gaspar","sequence":"additional","affiliation":[{"name":"CICECO\u2014Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, Campus Universit\u00e1rio de Santiago, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2342-3765","authenticated-orcid":false,"given":"Jo\u00e3o F.","family":"Mano","sequence":"additional","affiliation":[{"name":"CICECO\u2014Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, Campus Universit\u00e1rio de Santiago, 3810-193 Aveiro, Portugal"}]},{"given":"C. Joana","family":"Marques","sequence":"additional","affiliation":[{"name":"Genetics Unit, Department of Pathology, Faculty of Medicine, University of Porto (FMUP), Alameda Prof. Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"i3S-Institute for Research and Innovation in Health, University of Porto, R. Alfredo Allen 208, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3171-4666","authenticated-orcid":false,"given":"Rui","family":"Henrique","sequence":"additional","affiliation":[{"name":"Cancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP)\/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Center (Porto.CCC) Raquel Seruca, R. Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Department of Pathology, Portuguese Oncology Institute of Porto (IPO Porto), Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Department of Pathology and Molecular Immunology, ICBAS-School of Medicine and Biomedical Sciences, University of Porto, Rua Jorge Viterbo Ferreira n\u00ba 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4186-5345","authenticated-orcid":false,"given":"Carmen","family":"Jer\u00f3nimo","sequence":"additional","affiliation":[{"name":"Cancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP)\/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Center (Porto.CCC) Raquel Seruca, R. Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Department of Pathology and Molecular Immunology, ICBAS-School of Medicine and Biomedical Sciences, University of Porto, Rua Jorge Viterbo Ferreira n\u00ba 228, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21708","article-title":"Cancer statistics, 2022","volume":"72","author":"Siegel","year":"2022","journal-title":"CA A Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1210\/edrv.23.2.0460","article-title":"Androgen receptor (AR) coregulators: An overview","volume":"23","author":"Heinlein","year":"2002","journal-title":"Endocr. 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