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RNA-Seq transcriptome analysis shows anti-tumor actions of melatonin in a breast cancer xenograft model

Melatonin is a pleiotropic anti-cancer molecule that controls cancer growth by multiple mechanisms. RNA-Seq can potentially evaluate therapeutic response and its use in xenograft tumor models can differentiate the changes that occur specifically in tumor cells or in the tumor microenvironment (TME)....

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Autores principales: Jardim-Perassi, Bruna Victorasso, Alexandre, Pâmela A., Sonehara, Nathalia M., de Paula-Junior, Rubens, Reis Júnior, Osvaldo, Fukumasu, Heidge, Chammas, Roger, Coutinho, Luiz Lehmann, Zuccari, Debora Aparecida Pires de Campos
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6353949/
https://www.ncbi.nlm.nih.gov/pubmed/30700756
http://dx.doi.org/10.1038/s41598-018-37413-w
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author Jardim-Perassi, Bruna Victorasso
Alexandre, Pâmela A.
Sonehara, Nathalia M.
de Paula-Junior, Rubens
Reis Júnior, Osvaldo
Fukumasu, Heidge
Chammas, Roger
Coutinho, Luiz Lehmann
Zuccari, Debora Aparecida Pires de Campos
author_facet Jardim-Perassi, Bruna Victorasso
Alexandre, Pâmela A.
Sonehara, Nathalia M.
de Paula-Junior, Rubens
Reis Júnior, Osvaldo
Fukumasu, Heidge
Chammas, Roger
Coutinho, Luiz Lehmann
Zuccari, Debora Aparecida Pires de Campos
author_sort Jardim-Perassi, Bruna Victorasso
collection PubMed
description Melatonin is a pleiotropic anti-cancer molecule that controls cancer growth by multiple mechanisms. RNA-Seq can potentially evaluate therapeutic response and its use in xenograft tumor models can differentiate the changes that occur specifically in tumor cells or in the tumor microenvironment (TME). Melatonin actions were evaluated in a xenograft model of triple-negative breast cancer. Balb/c nude mice bearing MDA-MB-231 tumors were treated with melatonin or vehicle. RNA-Seq was performed on the Illumina HiSeq. 2500 and data were mapped against human and mouse genomes separately to differentiate species-specific expression. Differentially expressed (DE) genes were identified and Weighted Gene Co-expression Network Analysis (WGCNA) was used to detect clusters of highly co-expressed genes. Melatonin treatment reduced tumor growth (p < 0.01). 57 DE genes were identified in murine cells, which represented the TME, and were mainly involved in immune response. The WGCNA detected co-expressed genes in tumor cells and TME, which were related to the immune system among other biological processes. The upregulation of two genes (Tnfaip8l2 and Il1f6) by melatonin was validated in the TME, these genes play important roles in the immune system. Taken together, the transcriptomic data suggests that melatonin anti-tumor actions occur through modulation of TME in this xenograft tumor model.
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spelling pubmed-63539492019-02-01 RNA-Seq transcriptome analysis shows anti-tumor actions of melatonin in a breast cancer xenograft model Jardim-Perassi, Bruna Victorasso Alexandre, Pâmela A. Sonehara, Nathalia M. de Paula-Junior, Rubens Reis Júnior, Osvaldo Fukumasu, Heidge Chammas, Roger Coutinho, Luiz Lehmann Zuccari, Debora Aparecida Pires de Campos Sci Rep Article Melatonin is a pleiotropic anti-cancer molecule that controls cancer growth by multiple mechanisms. RNA-Seq can potentially evaluate therapeutic response and its use in xenograft tumor models can differentiate the changes that occur specifically in tumor cells or in the tumor microenvironment (TME). Melatonin actions were evaluated in a xenograft model of triple-negative breast cancer. Balb/c nude mice bearing MDA-MB-231 tumors were treated with melatonin or vehicle. RNA-Seq was performed on the Illumina HiSeq. 2500 and data were mapped against human and mouse genomes separately to differentiate species-specific expression. Differentially expressed (DE) genes were identified and Weighted Gene Co-expression Network Analysis (WGCNA) was used to detect clusters of highly co-expressed genes. Melatonin treatment reduced tumor growth (p < 0.01). 57 DE genes were identified in murine cells, which represented the TME, and were mainly involved in immune response. The WGCNA detected co-expressed genes in tumor cells and TME, which were related to the immune system among other biological processes. The upregulation of two genes (Tnfaip8l2 and Il1f6) by melatonin was validated in the TME, these genes play important roles in the immune system. Taken together, the transcriptomic data suggests that melatonin anti-tumor actions occur through modulation of TME in this xenograft tumor model. Nature Publishing Group UK 2019-01-30 /pmc/articles/PMC6353949/ /pubmed/30700756 http://dx.doi.org/10.1038/s41598-018-37413-w Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Jardim-Perassi, Bruna Victorasso
Alexandre, Pâmela A.
Sonehara, Nathalia M.
de Paula-Junior, Rubens
Reis Júnior, Osvaldo
Fukumasu, Heidge
Chammas, Roger
Coutinho, Luiz Lehmann
Zuccari, Debora Aparecida Pires de Campos
RNA-Seq transcriptome analysis shows anti-tumor actions of melatonin in a breast cancer xenograft model
title RNA-Seq transcriptome analysis shows anti-tumor actions of melatonin in a breast cancer xenograft model
title_full RNA-Seq transcriptome analysis shows anti-tumor actions of melatonin in a breast cancer xenograft model
title_fullStr RNA-Seq transcriptome analysis shows anti-tumor actions of melatonin in a breast cancer xenograft model
title_full_unstemmed RNA-Seq transcriptome analysis shows anti-tumor actions of melatonin in a breast cancer xenograft model
title_short RNA-Seq transcriptome analysis shows anti-tumor actions of melatonin in a breast cancer xenograft model
title_sort rna-seq transcriptome analysis shows anti-tumor actions of melatonin in a breast cancer xenograft model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6353949/
https://www.ncbi.nlm.nih.gov/pubmed/30700756
http://dx.doi.org/10.1038/s41598-018-37413-w
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