microRNAs as biomarkers of cancer drug resistance
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Tipo de documento: | Dissertação |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10362/114349 |
Resumo: | Cancer drug resistance (CDR) is a central problem in therapeutic failure. Several mechanisms can underlie CDR, including increased expression and activity of efflux ABC transporters and epigenetic phenomena. A topic that is not usually addressed is the mechanism underlying the loss of resistance to therapy once the challenge to these cells is withdrawn. A KCR cell line (doxorubicin-resistant and expressing ABCB1) was used to induce loss of resistance by withdrawing doxorubicin in culture medium, assess ABCB1 expression and activity and determine a signature of microRNAs expression. The activity of ABCB1 was analysed by fluorescence microscopy and flow cytometry through fluorescence (DiOC2) substrate retention assays. Expression of 1008 microRNAs was assessed before and after doxorubicin withdrawal. After 16 weeks of doxorubicin withdrawal we observed a decrease of ABCB1 activity and expression. Moreover, we determined a signature of 23 microRNAs, 13 under-expressed and 10 over expressed, 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 pathways in loss of CDR. Taken together, the data reported reinforces the assumption that ABCB1 may play 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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microRNAs as biomarkers of cancer drug resistanceBreast cancerDoxorubicinCancer Drug ResistanceABCB1 transportersmicroRNAsDomínio/Área Científica::Engenharia e Tecnologia::Outras Engenharias e TecnologiasCancer drug resistance (CDR) is a central problem in therapeutic failure. Several mechanisms can underlie CDR, including increased expression and activity of efflux ABC transporters and epigenetic phenomena. A topic that is not usually addressed is the mechanism underlying the loss of resistance to therapy once the challenge to these cells is withdrawn. A KCR cell line (doxorubicin-resistant and expressing ABCB1) was used to induce loss of resistance by withdrawing doxorubicin in culture medium, assess ABCB1 expression and activity and determine a signature of microRNAs expression. The activity of ABCB1 was analysed by fluorescence microscopy and flow cytometry through fluorescence (DiOC2) substrate retention assays. Expression of 1008 microRNAs was assessed before and after doxorubicin withdrawal. After 16 weeks of doxorubicin withdrawal we observed a decrease of ABCB1 activity and expression. Moreover, we determined a signature of 23 microRNAs, 13 under-expressed and 10 over expressed, 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 pathways in loss of CDR. Taken together, the data reported reinforces the assumption that ABCB1 may play a major role in the kinetics of CDR and their levels of expression are in the dependence of the circuitry of cell miRNAs.Rodrigues, SebastiãoGomes, BrunoRUNHonrado, Mónica Gabriela dos Santos2021-03-24T11:19:42Z2020-0720202020-07-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10362/114349enginfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T04:57:02Zoai:run.unl.pt:10362/114349Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:42:30.401199Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
microRNAs as biomarkers of cancer drug resistance |
title |
microRNAs as biomarkers of cancer drug resistance |
spellingShingle |
microRNAs as biomarkers of cancer drug resistance Honrado, Mónica Gabriela dos Santos Breast cancer Doxorubicin Cancer Drug Resistance ABCB1 transporters microRNAs Domínio/Área Científica::Engenharia e Tecnologia::Outras Engenharias e Tecnologias |
title_short |
microRNAs as biomarkers of cancer drug resistance |
title_full |
microRNAs as biomarkers of cancer drug resistance |
title_fullStr |
microRNAs as biomarkers of cancer drug resistance |
title_full_unstemmed |
microRNAs as biomarkers of cancer drug resistance |
title_sort |
microRNAs as biomarkers of cancer drug resistance |
author |
Honrado, Mónica Gabriela dos Santos |
author_facet |
Honrado, Mónica Gabriela dos Santos |
author_role |
author |
dc.contributor.none.fl_str_mv |
Rodrigues, Sebastião Gomes, Bruno RUN |
dc.contributor.author.fl_str_mv |
Honrado, Mónica Gabriela dos Santos |
dc.subject.por.fl_str_mv |
Breast cancer Doxorubicin Cancer Drug Resistance ABCB1 transporters microRNAs Domínio/Área Científica::Engenharia e Tecnologia::Outras Engenharias e Tecnologias |
topic |
Breast cancer Doxorubicin Cancer Drug Resistance ABCB1 transporters microRNAs Domínio/Área Científica::Engenharia e Tecnologia::Outras Engenharias e Tecnologias |
description |
Cancer drug resistance (CDR) is a central problem in therapeutic failure. Several mechanisms can underlie CDR, including increased expression and activity of efflux ABC transporters and epigenetic phenomena. A topic that is not usually addressed is the mechanism underlying the loss of resistance to therapy once the challenge to these cells is withdrawn. A KCR cell line (doxorubicin-resistant and expressing ABCB1) was used to induce loss of resistance by withdrawing doxorubicin in culture medium, assess ABCB1 expression and activity and determine a signature of microRNAs expression. The activity of ABCB1 was analysed by fluorescence microscopy and flow cytometry through fluorescence (DiOC2) substrate retention assays. Expression of 1008 microRNAs was assessed before and after doxorubicin withdrawal. After 16 weeks of doxorubicin withdrawal we observed a decrease of ABCB1 activity and expression. Moreover, we determined a signature of 23 microRNAs, 13 under-expressed and 10 over expressed, 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 pathways in loss of CDR. Taken together, the data reported reinforces the assumption that ABCB1 may play a major role in the kinetics of CDR and their levels of expression are in the dependence of the circuitry of cell miRNAs. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-07 2020 2020-07-01T00:00:00Z 2021-03-24T11:19:42Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10362/114349 |
url |
http://hdl.handle.net/10362/114349 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799138036318994432 |