{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T18:17:11Z","timestamp":1762021031541,"version":"build-2065373602"},"reference-count":47,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,4,23]],"date-time":"2020-04-23T00:00:00Z","timestamp":1587600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UID-BIM-00009-2020"],"award-info":[{"award-number":["UID-BIM-00009-2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cancer drug resistance (CDR) is a major problem in therapeutic failure. Over 90% of patients with metastatic cancer present CDR. Several mechanisms underlie CDR, including the increased expression of efflux ABC transporters and epigenetic phenomena. Nevertheless, a topic that is not usually addressed is the mechanism underlying the loss of CDR once the challenge to these cells is withdrawn. A KCR cell line (doxorubicin-resistant, expressing ABCB1) was used to induce loss of resistance by withdrawing doxorubicin in culture medium. ABCB1 activity was analysed by fluorescence microscopy and flow cytometry through substrate (DiOC2) retention assays. The expression of 1008 microRNAs was assessed before and after doxorubicin withdrawal. After 16 weeks of doxorubicin withdrawal, a decrease of ABCB1 activity and expression occurred. Moreover, we determined a signature of 23 microRNAs, 13 underexpressed and 10 overexpressed, as a tool to assess loss of resistance. Through pathway enrichment analysis, \u201cPathways in cancer\u201d, \u201cProteoglycans in cancer\u201d and \u201cECM-receptor interaction\u201d were identified as relevant in the loss of CDR. Taken together, the data reinforce the assumption that ABCB1 plays a major role in the kinetics of CDR, and their levels of expression are in the dependence of the circuitry of cell miRNAs.<\/jats:p>","DOI":"10.3390\/ijms21082985","type":"journal-article","created":{"date-parts":[[2020,4,23]],"date-time":"2020-04-23T10:46:22Z","timestamp":1587638782000},"page":"2985","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["ABC Efflux Transporters and the Circuitry of miRNAs: Kinetics of Expression in Cancer Drug Resistance"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5632-1095","authenticated-orcid":false,"given":"Bruno C.","family":"Gomes","sequence":"first","affiliation":[{"name":"Centre for Toxicogenomics and Human Health; Genetics, Oncology and Human Toxicology, NOVA Medical School, Universidade NOVA de Lisboa, Rua C\u00e2mara Pestana 6, 1150-008 Lisbon, Portugal"}]},{"given":"M\u00f3nica","family":"Honrado","sequence":"additional","affiliation":[{"name":"Centre for Toxicogenomics and Human Health; Genetics, Oncology and Human Toxicology, NOVA Medical School, Universidade NOVA de Lisboa, Rua C\u00e2mara Pestana 6, 1150-008 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5066-9982","authenticated-orcid":false,"given":"Ana","family":"Armada","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine, Instituto de Higiene e Medicina Tropical, Universidade NOVA de Lisboa, Rua da Junqueira 100, 1349-008 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9676-6251","authenticated-orcid":false,"given":"Miguel","family":"Viveiros","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine, Instituto de Higiene e Medicina Tropical, Universidade NOVA de Lisboa, Rua da Junqueira 100, 1349-008 Lisbon, Portugal"}]},{"given":"Jos\u00e9","family":"Rueff","sequence":"additional","affiliation":[{"name":"Centre for Toxicogenomics and Human Health; Genetics, Oncology and Human Toxicology, NOVA Medical School, Universidade NOVA de Lisboa, Rua C\u00e2mara Pestana 6, 1150-008 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8139-4595","authenticated-orcid":false,"given":"Ant\u00f3nio S.","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Centre for Toxicogenomics and Human Health; Genetics, Oncology and Human Toxicology, NOVA Medical School, Universidade NOVA de Lisboa, Rua C\u00e2mara Pestana 6, 1150-008 Lisbon, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-4939-3347-1_1","article-title":"Cancer Drug Resistance: A Brief Overview from a Genetic Viewpoint","volume":"1395","author":"Rueff","year":"2016","journal-title":"Methods Mol. 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