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ABC Efflux Transporters and the Circuitry of miRNAs: Kinetics of Expression in Cancer Drug Resistance

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 addresse...

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Autores principales: Gomes, Bruno C., Honrado, Mónica, Armada, Ana, Viveiros, Miguel, Rueff, José, Rodrigues, António S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215654/
https://www.ncbi.nlm.nih.gov/pubmed/32340269
http://dx.doi.org/10.3390/ijms21082985
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author Gomes, Bruno C.
Honrado, Mónica
Armada, Ana
Viveiros, Miguel
Rueff, José
Rodrigues, António S.
author_facet Gomes, Bruno C.
Honrado, Mónica
Armada, Ana
Viveiros, Miguel
Rueff, José
Rodrigues, António S.
author_sort Gomes, Bruno C.
collection PubMed
description 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a topic that is not usually addressed is the mechanism underlying the loss of CDR once the challenge to these cells is withdrawn.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, “Pathways in cancer”, “Proteoglycans in cancer” and “ECM-receptor interaction” 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.
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spelling pubmed-72156542020-05-22 ABC Efflux Transporters and the Circuitry of miRNAs: Kinetics of Expression in Cancer Drug Resistance Gomes, Bruno C. Honrado, Mónica Armada, Ana Viveiros, Miguel Rueff, José Rodrigues, António S. Int J Mol Sci Article 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, “Pathways in cancer”, “Proteoglycans in cancer” and “ECM-receptor interaction” 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. MDPI 2020-04-23 /pmc/articles/PMC7215654/ /pubmed/32340269 http://dx.doi.org/10.3390/ijms21082985 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gomes, Bruno C.
Honrado, Mónica
Armada, Ana
Viveiros, Miguel
Rueff, José
Rodrigues, António S.
ABC Efflux Transporters and the Circuitry of miRNAs: Kinetics of Expression in Cancer Drug Resistance
title ABC Efflux Transporters and the Circuitry of miRNAs: Kinetics of Expression in Cancer Drug Resistance
title_full ABC Efflux Transporters and the Circuitry of miRNAs: Kinetics of Expression in Cancer Drug Resistance
title_fullStr ABC Efflux Transporters and the Circuitry of miRNAs: Kinetics of Expression in Cancer Drug Resistance
title_full_unstemmed ABC Efflux Transporters and the Circuitry of miRNAs: Kinetics of Expression in Cancer Drug Resistance
title_short ABC Efflux Transporters and the Circuitry of miRNAs: Kinetics of Expression in Cancer Drug Resistance
title_sort abc efflux transporters and the circuitry of mirnas: kinetics of expression in cancer drug resistance
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215654/
https://www.ncbi.nlm.nih.gov/pubmed/32340269
http://dx.doi.org/10.3390/ijms21082985
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