{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T19:24:04Z","timestamp":1770492244723,"version":"3.49.0"},"reference-count":56,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,10,7]],"date-time":"2022-10-07T00:00:00Z","timestamp":1665100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"S\u00e3o Paulo Research Foundation (FAPESP)","award":["2013\/08135-2"],"award-info":[{"award-number":["2013\/08135-2"]}]},{"name":"S\u00e3o Paulo Research Foundation (FAPESP)","award":["2014\/02493-7"],"award-info":[{"award-number":["2014\/02493-7"]}]},{"name":"S\u00e3o Paulo Research Foundation (FAPESP)","award":["2022\/13176-9"],"award-info":[{"award-number":["2022\/13176-9"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES)-Finance Code 001","award":["2013\/08135-2"],"award-info":[{"award-number":["2013\/08135-2"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES)-Finance Code 001","award":["2014\/02493-7"],"award-info":[{"award-number":["2014\/02493-7"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES)-Finance Code 001","award":["2022\/13176-9"],"award-info":[{"award-number":["2022\/13176-9"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq)","award":["2013\/08135-2"],"award-info":[{"award-number":["2013\/08135-2"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq)","award":["2014\/02493-7"],"award-info":[{"award-number":["2014\/02493-7"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq)","award":["2022\/13176-9"],"award-info":[{"award-number":["2022\/13176-9"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Despite advances in diagnostic and therapeutic approaches for lung cancer, new therapies targeting metastasis by the specific regulation of cancer genes are needed. In this study, we screened a small library of epigenetic inhibitors in non-small-cell lung cancer (NSCLC) cell lines and evaluated 38 epigenetic targets for their potential role in metastatic NSCLC. The potential candidates were ranked by a streamlined approach using in silico and in vitro experiments based on publicly available databases and evaluated by real-time qPCR target gene expression, cell viability and invasion assays, and transcriptomic analysis. The survival rate of patients with lung adenocarcinoma is inversely correlated with the gene expression of eight epigenetic targets, and a systematic review of the literature confirmed that four of them have already been identified as targets for the treatment of NSCLC. Using nontoxic doses of the remaining inhibitors, KDM6B and PADI4 were identified as potential targets affecting the invasion and migration of metastatic lung cancer cell lines. Transcriptomic analysis of KDM6B and PADI4 treated cells showed altered expression of important genes related to the metastatic process. In conclusion, we showed that KDM6B and PADI4 are promising targets for inhibiting the metastasis of lung adenocarcinoma cancer cells.<\/jats:p>","DOI":"10.3390\/ijms231911911","type":"journal-article","created":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T23:39:31Z","timestamp":1665272371000},"page":"11911","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["A Screening of Epigenetic Therapeutic Targets for Non-Small Cell Lung Cancer Reveals PADI4 and KDM6B as Promising Candidates"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9865-8983","authenticated-orcid":false,"given":"J\u00e9ssika Cristina Chagas","family":"Lesbon","sequence":"first","affiliation":[{"name":"Laboratory of Comparative and Translational Oncology, Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of S\u00e3o Paulo, Duque de Caxias, 225-Jardim Elite, Pirassununga 13635-900, SP, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9880-7755","authenticated-orcid":false,"given":"Taismara Kustro","family":"Garnica","sequence":"additional","affiliation":[{"name":"Laboratory of Comparative and Translational Oncology, Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of S\u00e3o Paulo, Duque de Caxias, 225-Jardim Elite, Pirassununga 13635-900, SP, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2435-9822","authenticated-orcid":false,"given":"Pedro Luiz Porf\u00edrio","family":"Xavier","sequence":"additional","affiliation":[{"name":"Laboratory of Comparative and Translational Oncology, Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of S\u00e3o Paulo, Duque de Caxias, 225-Jardim Elite, Pirassununga 13635-900, SP, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1225-1953","authenticated-orcid":false,"given":"Arina L\u00e1zaro","family":"Rochetti","sequence":"additional","affiliation":[{"name":"Laboratory of Comparative and Translational Oncology, Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of S\u00e3o Paulo, Duque de Caxias, 225-Jardim Elite, Pirassununga 13635-900, SP, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9639-7940","authenticated-orcid":false,"given":"Rui Manuel","family":"Reis","sequence":"additional","affiliation":[{"name":"Molecular Oncology Research Center, Hospital de Amor, Antenor Duarte Vil\u00e9la, 1331-Dr. Paulo Prata, Barretos 14784-400, SP, Brazil"},{"name":"Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, 4805-017 Guimar\u00e3es, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2402-4157","authenticated-orcid":false,"given":"Susanne","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Structural Genomics Consortium, Buchmann Institute for Molecular Life Sciences, Johann Wolfgang Goethe University, Max-von-Laue-Str 15-60438, 60438 Frankfurt am Main, Germany"}]},{"given":"Heidge","family":"Fukumasu","sequence":"additional","affiliation":[{"name":"Laboratory of Comparative and Translational Oncology, Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of S\u00e3o Paulo, Duque de Caxias, 225-Jardim Elite, Pirassununga 13635-900, SP, Brazil"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. 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