Ação antimetastática da melatonina pela modulação de microRNAs candidatos em linhagens de câncer de mama
Autor(a) principal: | |
---|---|
Data de Publicação: | 2018 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da FAMERP |
Texto Completo: | http://bdtd.famerp.br/handle/tede/538 |
Resumo: | Breast cancer presents high incidence and death rates worldwide. Metastasis is one of the main causes of high mortality rates by this neoplasm. MicroRNAs (miRNAs) are small non-coding RNA molecules with nearly 18-22 nucleotides, involved in gene expression regulation. Studies demonstrate the role this molecules in tumor progression, including breast cancer. Melatonin, a hormone secreted mainly in pineal gland, has been presenting several effects in cancer regulation, acting on the modulation of proteins and miRNAs. Aim: The aim of the present study was to investigate the action of melatonin on miRNA-10a-5p modulation in triple-negative breast cancer cells (TNBC), and associating with tumor progression. Materials and Methods: The MTT (3- (4,5-Dimethylthiazol-2-yl) -2,5-Diphenyltetrazolium Bromide) assay was performed to verify cell viability of MDA-MB-468 cells at different concentrations of melatonin for 24 hours. The differential expression of 84 miRNAs associated with breast cancer was verified by PCR-Array. The miR-10a was selected for its involvement with tumor process and its gene expression and its target HOXD10 were verified by real-time PCR in breast cancer cell lines. The following groups were considered: cells treated or not with melatonin; transfected with inhibition of miR-10a or negative control of reaction. The invasion and migration assay using matrigel inserts was performed and protein expression of epithelial-mesenchymal transition (EMT), Ecadherin, claudin 7 and vimentin markers were investigated, as PIK3CA proliferation marker, by Western blotting. Results: Our results showed that 1 mM melatonin significantly decreased cell viability. The results of PCR Array showed thirteen miRNAs modulated by melatonin (six overexpressed and seven inhibited). The gene expression showed a decrease in relative amount of miR-10a and its target HOXD10 after melatonin treatmet. The matrigel assays showed that melatonin and inhibition of miR-10a decreased the cell invasion and migration. According to the protein analysis, melatonin was able to reduce the expression of vimentin and claudin 7 proteins and increase E-cadherin expression. On the other hand, inhibition of miR-10a reduced the vimentin protein and did not modulate claudin 7 and E-cadherin. Conclusion: In this study was verified the ability of melatonin modulating miRNAs expression by decreasing miR-10a, affecting tumor invasion and migration, and proteins involved with EMT. In this way, we support the idea of the potential role of melatonin in the regulation of metastasis. |
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Zuccari, Debora Aparecida Pires de Camposhttp://lattes.cnpq.br/3299100010535257Antonucci, Gilmara Ausechhttp://lattes.cnpq.br/6611576348045116Pavarino, Érika Cristinahttp://lattes.cnpq.br/061201439935044740064188841http://lattes.cnpq.br/8901490678564304Oliveira, Jéssica Gisleine de2019-06-05T17:15:21Z2018-10-19Oliveira, Jéssica Gisleine de. Ação antimetastática da melatonina pela modulação de microRNAs candidatos em linhagens de câncer de mama. 2018. 136 f. Dissertação (Programa de Pós-Graduação em Ciências da Saúde) - Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto.1412http://bdtd.famerp.br/handle/tede/538Breast cancer presents high incidence and death rates worldwide. Metastasis is one of the main causes of high mortality rates by this neoplasm. MicroRNAs (miRNAs) are small non-coding RNA molecules with nearly 18-22 nucleotides, involved in gene expression regulation. Studies demonstrate the role this molecules in tumor progression, including breast cancer. Melatonin, a hormone secreted mainly in pineal gland, has been presenting several effects in cancer regulation, acting on the modulation of proteins and miRNAs. Aim: The aim of the present study was to investigate the action of melatonin on miRNA-10a-5p modulation in triple-negative breast cancer cells (TNBC), and associating with tumor progression. Materials and Methods: The MTT (3- (4,5-Dimethylthiazol-2-yl) -2,5-Diphenyltetrazolium Bromide) assay was performed to verify cell viability of MDA-MB-468 cells at different concentrations of melatonin for 24 hours. The differential expression of 84 miRNAs associated with breast cancer was verified by PCR-Array. The miR-10a was selected for its involvement with tumor process and its gene expression and its target HOXD10 were verified by real-time PCR in breast cancer cell lines. The following groups were considered: cells treated or not with melatonin; transfected with inhibition of miR-10a or negative control of reaction. The invasion and migration assay using matrigel inserts was performed and protein expression of epithelial-mesenchymal transition (EMT), Ecadherin, claudin 7 and vimentin markers were investigated, as PIK3CA proliferation marker, by Western blotting. Results: Our results showed that 1 mM melatonin significantly decreased cell viability. The results of PCR Array showed thirteen miRNAs modulated by melatonin (six overexpressed and seven inhibited). The gene expression showed a decrease in relative amount of miR-10a and its target HOXD10 after melatonin treatmet. The matrigel assays showed that melatonin and inhibition of miR-10a decreased the cell invasion and migration. According to the protein analysis, melatonin was able to reduce the expression of vimentin and claudin 7 proteins and increase E-cadherin expression. On the other hand, inhibition of miR-10a reduced the vimentin protein and did not modulate claudin 7 and E-cadherin. Conclusion: In this study was verified the ability of melatonin modulating miRNAs expression by decreasing miR-10a, affecting tumor invasion and migration, and proteins involved with EMT. In this way, we support the idea of the potential role of melatonin in the regulation of metastasis.O câncer de mama apresenta elevadas taxas de incidência e mortalidade em todo o mundo. Um dos principais fatores responsáveis pelos altos índices de mortalidade desta neoplasia é a metástase. Os microRNAs (miRNAs) são pequenas moléculas de RNA não codificantes com cerca de 18-22 nucleotídeos, envolvidos com a regulação da expressão gênica. Estudos demonstram o papel dessas moléculas na progressão tumoral, em especial do câncer de mama. A melatonina, um hormônio secretado principalmente pela glândula pineal vem mostrando diversos efeitos na regulação do câncer, atuando na modulação de proteínas e miRNAs. Objetivo: O objetivo do presente estudo foi investigar a ação da melatonina na modulação do miRNA-10a-5p (mir-10a) em células de linhagem de câncer de mama triplo-negativo (TNBC), e associar com a progressão tumoral. Material e Método: O ensaio de MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) foi realizado para verificar a viabilidade celular da linhagem MDA-MB-468 após o tratamento com melatonina em diferentes concentrações. A expressão diferencial de 84 miRNAs associados ao câncer de mama foi verificado por PCR-Array. O miR-10a foi selecionado por seu envolvimento com o processo tumoral e sua expressão gênica e de seu gene alvo HOXD10 foram verificados por PCR em tempo real em linhagens de câncer de mama. Os seguintes grupos foram considerados: células tratadas ou não com melatonina; transfectadas com inibição do miR-10a e o controle negativo da reação. O ensaio de invasão e migração utilizando insertos de matrigel foi realizado e a expressão proteica de marcadores da transição epitélio-mesenquimal (EMT), E-caderina, claudina 7 e vimentina foi investigada, assim como do marcador de proliferação PIK3CA, por Western blotting. Resultados: Nossos resultados mostraram que 1 mM de melatonina diminuiu significantemente a viabilidade celular. Os resultados de PCR Array mostraram treze miRNAs modulados pela melatonina (seis superexpressos e sete inibidos). A expressão gênica mostrou diminuição da quantidade relativa do miR-10a e de seu gene alvo HOXD10 após tratamento com melatonina. O ensaio matrigel mostrou que a melatonina e a inibição do miR-10a diminuíram a invasão e migração das células. De acordo com a análise proteica, a melatonina foi capaz de reduzir a expressão das proteínas vimentina e claudina 7 e aumentar a expressão da E-caderina. Por outro lado, a inibição do miR-10a reduziu a proteína vimentina e não modulou claudina 7 e Ecaderina. Conclusão: Nesse trabalho verificou-se a habilidade da melatonina em modular a expressão de miRNAs, diminuindo o miR-10a, afetando a invasão e migração tumoral, além de proteínas envolvidas com a EMT, demonstrando seu potencial papel na regulação da metástase.Submitted by Suzana Dias (suzana.dias@famerp.br) on 2019-06-05T17:15:21Z No. of bitstreams: 1 JessicaGisleinedeOliveira_Dissert.pdf: 1592787 bytes, checksum: 18645ec11966579bb9b4623e073576f3 (MD5)Made available in DSpace on 2019-06-05T17:15:21Z (GMT). No. of bitstreams: 1 JessicaGisleinedeOliveira_Dissert.pdf: 1592787 bytes, checksum: 18645ec11966579bb9b4623e073576f3 (MD5) Previous issue date: 2018-10-19Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESapplication/pdfporFaculdade de Medicina de São José do Rio PretoPrograma de Pós-Graduação em Ciências da SaúdeFAMERPBrasilFaculdade 1::Departamento 1Transição Epitelial-MesenquimalGlândula PinealNeoplasias da MamaBreast NeoplasmsMicroRNAsEpithelial-Mesenchymal TransitionPineal GlandMicroRNAsCIENCIAS DA SAUDEAção antimetastática da melatonina pela modulação de microRNAs candidatos em linhagens de câncer de mamainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesis-695441085367880657450050060060030662648750962450687654494148233069292075167498588264571info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da FAMERPinstname:Faculdade de Medicina de São José do Rio Preto (FAMERP)instacron:FAMERPORIGINALJessicaGisleinedeOliveira_Dissert.pdfJessicaGisleinedeOliveira_Dissert.pdfapplication/pdf159278718645ec11966579bb9b4623e073576f3MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-82165bd3efa91386c1718a7f26a329fdcb468MD51http://bdtd.famerp.br/bitstream/tede/538/2/JessicaGisleinedeOliveira_Dissert.pdfhttp://bdtd.famerp.br/bitstream/tede/538/1/license.txttede/5382019-06-05 14:15:21.563oai:localhost: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Biblioteca Digital de Teses e Dissertaçõeshttp://bdtd.famerp.br/PUBhttps://bdtd.famerp.br/oai/requestsbdc@famerp.br||joao.junior@famerp.bropendoar:47112019-06-05T17:15:21Biblioteca Digital de Teses e Dissertações da FAMERP - Faculdade de Medicina de São José do Rio Preto (FAMERP)false |
dc.title.por.fl_str_mv |
Ação antimetastática da melatonina pela modulação de microRNAs candidatos em linhagens de câncer de mama |
title |
Ação antimetastática da melatonina pela modulação de microRNAs candidatos em linhagens de câncer de mama |
spellingShingle |
Ação antimetastática da melatonina pela modulação de microRNAs candidatos em linhagens de câncer de mama Oliveira, Jéssica Gisleine de Transição Epitelial-Mesenquimal Glândula Pineal Neoplasias da Mama Breast Neoplasms MicroRNAs Epithelial-Mesenchymal Transition Pineal Gland MicroRNAs CIENCIAS DA SAUDE |
title_short |
Ação antimetastática da melatonina pela modulação de microRNAs candidatos em linhagens de câncer de mama |
title_full |
Ação antimetastática da melatonina pela modulação de microRNAs candidatos em linhagens de câncer de mama |
title_fullStr |
Ação antimetastática da melatonina pela modulação de microRNAs candidatos em linhagens de câncer de mama |
title_full_unstemmed |
Ação antimetastática da melatonina pela modulação de microRNAs candidatos em linhagens de câncer de mama |
title_sort |
Ação antimetastática da melatonina pela modulação de microRNAs candidatos em linhagens de câncer de mama |
author |
Oliveira, Jéssica Gisleine de |
author_facet |
Oliveira, Jéssica Gisleine de |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Zuccari, Debora Aparecida Pires de Campos |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/3299100010535257 |
dc.contributor.referee1.fl_str_mv |
Antonucci, Gilmara Ausech |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/6611576348045116 |
dc.contributor.referee2.fl_str_mv |
Pavarino, Érika Cristina |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/0612014399350447 |
dc.contributor.authorID.fl_str_mv |
40064188841 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/8901490678564304 |
dc.contributor.author.fl_str_mv |
Oliveira, Jéssica Gisleine de |
contributor_str_mv |
Zuccari, Debora Aparecida Pires de Campos Antonucci, Gilmara Ausech Pavarino, Érika Cristina |
dc.subject.por.fl_str_mv |
Transição Epitelial-Mesenquimal Glândula Pineal Neoplasias da Mama Breast Neoplasms MicroRNAs |
topic |
Transição Epitelial-Mesenquimal Glândula Pineal Neoplasias da Mama Breast Neoplasms MicroRNAs Epithelial-Mesenchymal Transition Pineal Gland MicroRNAs CIENCIAS DA SAUDE |
dc.subject.eng.fl_str_mv |
Epithelial-Mesenchymal Transition Pineal Gland MicroRNAs |
dc.subject.cnpq.fl_str_mv |
CIENCIAS DA SAUDE |
description |
Breast cancer presents high incidence and death rates worldwide. Metastasis is one of the main causes of high mortality rates by this neoplasm. MicroRNAs (miRNAs) are small non-coding RNA molecules with nearly 18-22 nucleotides, involved in gene expression regulation. Studies demonstrate the role this molecules in tumor progression, including breast cancer. Melatonin, a hormone secreted mainly in pineal gland, has been presenting several effects in cancer regulation, acting on the modulation of proteins and miRNAs. Aim: The aim of the present study was to investigate the action of melatonin on miRNA-10a-5p modulation in triple-negative breast cancer cells (TNBC), and associating with tumor progression. Materials and Methods: The MTT (3- (4,5-Dimethylthiazol-2-yl) -2,5-Diphenyltetrazolium Bromide) assay was performed to verify cell viability of MDA-MB-468 cells at different concentrations of melatonin for 24 hours. The differential expression of 84 miRNAs associated with breast cancer was verified by PCR-Array. The miR-10a was selected for its involvement with tumor process and its gene expression and its target HOXD10 were verified by real-time PCR in breast cancer cell lines. The following groups were considered: cells treated or not with melatonin; transfected with inhibition of miR-10a or negative control of reaction. The invasion and migration assay using matrigel inserts was performed and protein expression of epithelial-mesenchymal transition (EMT), Ecadherin, claudin 7 and vimentin markers were investigated, as PIK3CA proliferation marker, by Western blotting. Results: Our results showed that 1 mM melatonin significantly decreased cell viability. The results of PCR Array showed thirteen miRNAs modulated by melatonin (six overexpressed and seven inhibited). The gene expression showed a decrease in relative amount of miR-10a and its target HOXD10 after melatonin treatmet. The matrigel assays showed that melatonin and inhibition of miR-10a decreased the cell invasion and migration. According to the protein analysis, melatonin was able to reduce the expression of vimentin and claudin 7 proteins and increase E-cadherin expression. On the other hand, inhibition of miR-10a reduced the vimentin protein and did not modulate claudin 7 and E-cadherin. Conclusion: In this study was verified the ability of melatonin modulating miRNAs expression by decreasing miR-10a, affecting tumor invasion and migration, and proteins involved with EMT. In this way, we support the idea of the potential role of melatonin in the regulation of metastasis. |
publishDate |
2018 |
dc.date.issued.fl_str_mv |
2018-10-19 |
dc.date.accessioned.fl_str_mv |
2019-06-05T17:15:21Z |
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info:eu-repo/semantics/publishedVersion |
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Oliveira, Jéssica Gisleine de. Ação antimetastática da melatonina pela modulação de microRNAs candidatos em linhagens de câncer de mama. 2018. 136 f. Dissertação (Programa de Pós-Graduação em Ciências da Saúde) - Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto. |
dc.identifier.uri.fl_str_mv |
http://bdtd.famerp.br/handle/tede/538 |
dc.identifier.doi.por.fl_str_mv |
1412 |
identifier_str_mv |
Oliveira, Jéssica Gisleine de. Ação antimetastática da melatonina pela modulação de microRNAs candidatos em linhagens de câncer de mama. 2018. 136 f. Dissertação (Programa de Pós-Graduação em Ciências da Saúde) - Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto. 1412 |
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