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Non-Metastatic Cutaneous Melanoma Induces Chronodisruption in Central and Peripheral Circadian Clocks

The biological clock has received increasing interest due to its key role in regulating body homeostasis in a time-dependent manner. Cancer development and progression has been linked to a disrupted molecular clock; however, in melanoma, the role of the biological clock is largely unknown. We invest...

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Autores principales: de Assis, Leonardo Vinícius Monteiro, Moraes, Maria Nathália, Magalhães-Marques, Keila Karoline, Kinker, Gabriela Sarti, da Silveira Cruz-Machado, Sanseray, de Lauro Castrucci, Ana Maria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5979525/
https://www.ncbi.nlm.nih.gov/pubmed/29614021
http://dx.doi.org/10.3390/ijms19041065
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author de Assis, Leonardo Vinícius Monteiro
Moraes, Maria Nathália
Magalhães-Marques, Keila Karoline
Kinker, Gabriela Sarti
da Silveira Cruz-Machado, Sanseray
de Lauro Castrucci, Ana Maria
author_facet de Assis, Leonardo Vinícius Monteiro
Moraes, Maria Nathália
Magalhães-Marques, Keila Karoline
Kinker, Gabriela Sarti
da Silveira Cruz-Machado, Sanseray
de Lauro Castrucci, Ana Maria
author_sort de Assis, Leonardo Vinícius Monteiro
collection PubMed
description The biological clock has received increasing interest due to its key role in regulating body homeostasis in a time-dependent manner. Cancer development and progression has been linked to a disrupted molecular clock; however, in melanoma, the role of the biological clock is largely unknown. We investigated the effects of the tumor on its micro- (TME) and macro-environments (TMaE) in a non-metastatic melanoma model. C57BL/6J mice were inoculated with murine B16-F10 melanoma cells and 2 weeks later the animals were euthanized every 6 h during 24 h. The presence of a localized tumor significantly impaired the biological clock of tumor-adjacent skin and affected the oscillatory expression of genes involved in light- and thermo-reception, proliferation, melanogenesis, and DNA repair. The expression of tumor molecular clock was significantly reduced compared to healthy skin but still displayed an oscillatory profile. We were able to cluster the affected genes using a human database and distinguish between primary melanoma and healthy skin. The molecular clocks of lungs and liver (common sites of metastasis), and the suprachiasmatic nucleus (SCN) were significantly affected by tumor presence, leading to chronodisruption in each organ. Taken altogether, the presence of non-metastatic melanoma significantly impairs the organism’s biological clocks. We suggest that the clock alterations found in TME and TMaE could impact development, progression, and metastasis of melanoma; thus, making the molecular clock an interesting pharmacological target.
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spelling pubmed-59795252018-06-10 Non-Metastatic Cutaneous Melanoma Induces Chronodisruption in Central and Peripheral Circadian Clocks de Assis, Leonardo Vinícius Monteiro Moraes, Maria Nathália Magalhães-Marques, Keila Karoline Kinker, Gabriela Sarti da Silveira Cruz-Machado, Sanseray de Lauro Castrucci, Ana Maria Int J Mol Sci Article The biological clock has received increasing interest due to its key role in regulating body homeostasis in a time-dependent manner. Cancer development and progression has been linked to a disrupted molecular clock; however, in melanoma, the role of the biological clock is largely unknown. We investigated the effects of the tumor on its micro- (TME) and macro-environments (TMaE) in a non-metastatic melanoma model. C57BL/6J mice were inoculated with murine B16-F10 melanoma cells and 2 weeks later the animals were euthanized every 6 h during 24 h. The presence of a localized tumor significantly impaired the biological clock of tumor-adjacent skin and affected the oscillatory expression of genes involved in light- and thermo-reception, proliferation, melanogenesis, and DNA repair. The expression of tumor molecular clock was significantly reduced compared to healthy skin but still displayed an oscillatory profile. We were able to cluster the affected genes using a human database and distinguish between primary melanoma and healthy skin. The molecular clocks of lungs and liver (common sites of metastasis), and the suprachiasmatic nucleus (SCN) were significantly affected by tumor presence, leading to chronodisruption in each organ. Taken altogether, the presence of non-metastatic melanoma significantly impairs the organism’s biological clocks. We suggest that the clock alterations found in TME and TMaE could impact development, progression, and metastasis of melanoma; thus, making the molecular clock an interesting pharmacological target. MDPI 2018-04-03 /pmc/articles/PMC5979525/ /pubmed/29614021 http://dx.doi.org/10.3390/ijms19041065 Text en © 2018 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
de Assis, Leonardo Vinícius Monteiro
Moraes, Maria Nathália
Magalhães-Marques, Keila Karoline
Kinker, Gabriela Sarti
da Silveira Cruz-Machado, Sanseray
de Lauro Castrucci, Ana Maria
Non-Metastatic Cutaneous Melanoma Induces Chronodisruption in Central and Peripheral Circadian Clocks
title Non-Metastatic Cutaneous Melanoma Induces Chronodisruption in Central and Peripheral Circadian Clocks
title_full Non-Metastatic Cutaneous Melanoma Induces Chronodisruption in Central and Peripheral Circadian Clocks
title_fullStr Non-Metastatic Cutaneous Melanoma Induces Chronodisruption in Central and Peripheral Circadian Clocks
title_full_unstemmed Non-Metastatic Cutaneous Melanoma Induces Chronodisruption in Central and Peripheral Circadian Clocks
title_short Non-Metastatic Cutaneous Melanoma Induces Chronodisruption in Central and Peripheral Circadian Clocks
title_sort non-metastatic cutaneous melanoma induces chronodisruption in central and peripheral circadian clocks
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5979525/
https://www.ncbi.nlm.nih.gov/pubmed/29614021
http://dx.doi.org/10.3390/ijms19041065
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