Transcriptome Analysis of Canine Cutaneous Melanoma and Melanocytoma Reveals a Modulation of Genes Regulating Extracellular Matrix Metabolism and Cell Cycle

Abstract Interactions between tumor cells and tumor microenvironment are considered critical in carcinogenesis, tumor invasion and metastasis. To examine transcriptome changes and to explore the relationship with tumor microenvironment in canine cutaneous melanocytoma and melanoma, we extracted RNA...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Chiara Brachelente, Katia Cappelli, Stefano Capomaccio, Ilaria Porcellato, Serenella Silvestri, Laura Bongiovanni, Raffaella De Maria, Andrea Verini Supplizi, Luca Mechelli, Monica Sforna
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2017
Materias:
R
Q
Acceso en línea:https://doaj.org/article/4d21a72599b74ab18450ea884c9a4555
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:4d21a72599b74ab18450ea884c9a4555
record_format dspace
spelling oai:doaj.org-article:4d21a72599b74ab18450ea884c9a45552021-12-02T12:32:50ZTranscriptome Analysis of Canine Cutaneous Melanoma and Melanocytoma Reveals a Modulation of Genes Regulating Extracellular Matrix Metabolism and Cell Cycle10.1038/s41598-017-06281-12045-2322https://doaj.org/article/4d21a72599b74ab18450ea884c9a45552017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06281-1https://doaj.org/toc/2045-2322Abstract Interactions between tumor cells and tumor microenvironment are considered critical in carcinogenesis, tumor invasion and metastasis. To examine transcriptome changes and to explore the relationship with tumor microenvironment in canine cutaneous melanocytoma and melanoma, we extracted RNA from formalin-fixed, paraffin-embedded (FFPE) specimens and analyzed them by means of RNA-seq for transcriptional analysis. Melanocytoma and melanoma samples were compared to detect differential gene expressions and significant enriched pathways were explored to reveal functional relations between differentially expressed genes. The study demonstrated a differential expression of 60 genes in melanomas compared to melanocytomas. The differentially expressed genes cluster in the extracellular matrix-receptor interaction, protein digestion and absorption, focal adhesion and PI3K-Akt (phosphoinositide 3-kinase/protein kinase B) signaling pathways. Genes encoding for several collagen proteins were more commonly differentially expressed. Results of the RNA-seq were validated by qRT-PCR and protein expression of some target molecules was investigated by means of immunohistochemistry. We hypothesize that the developing melanoma actively promotes collagen metabolism and extracellular matrix remodeling as well as enhancing cell proliferation and survival contributing to disease progression and metastasis. In this study, we also detected unidentified genes in human melanoma expression studies and uncover new candidate drug targets for further testing in canine melanoma.Chiara BrachelenteKatia CappelliStefano CapomaccioIlaria PorcellatoSerenella SilvestriLaura BongiovanniRaffaella De MariaAndrea Verini SuppliziLuca MechelliMonica SfornaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Chiara Brachelente
Katia Cappelli
Stefano Capomaccio
Ilaria Porcellato
Serenella Silvestri
Laura Bongiovanni
Raffaella De Maria
Andrea Verini Supplizi
Luca Mechelli
Monica Sforna
Transcriptome Analysis of Canine Cutaneous Melanoma and Melanocytoma Reveals a Modulation of Genes Regulating Extracellular Matrix Metabolism and Cell Cycle
description Abstract Interactions between tumor cells and tumor microenvironment are considered critical in carcinogenesis, tumor invasion and metastasis. To examine transcriptome changes and to explore the relationship with tumor microenvironment in canine cutaneous melanocytoma and melanoma, we extracted RNA from formalin-fixed, paraffin-embedded (FFPE) specimens and analyzed them by means of RNA-seq for transcriptional analysis. Melanocytoma and melanoma samples were compared to detect differential gene expressions and significant enriched pathways were explored to reveal functional relations between differentially expressed genes. The study demonstrated a differential expression of 60 genes in melanomas compared to melanocytomas. The differentially expressed genes cluster in the extracellular matrix-receptor interaction, protein digestion and absorption, focal adhesion and PI3K-Akt (phosphoinositide 3-kinase/protein kinase B) signaling pathways. Genes encoding for several collagen proteins were more commonly differentially expressed. Results of the RNA-seq were validated by qRT-PCR and protein expression of some target molecules was investigated by means of immunohistochemistry. We hypothesize that the developing melanoma actively promotes collagen metabolism and extracellular matrix remodeling as well as enhancing cell proliferation and survival contributing to disease progression and metastasis. In this study, we also detected unidentified genes in human melanoma expression studies and uncover new candidate drug targets for further testing in canine melanoma.
format article
author Chiara Brachelente
Katia Cappelli
Stefano Capomaccio
Ilaria Porcellato
Serenella Silvestri
Laura Bongiovanni
Raffaella De Maria
Andrea Verini Supplizi
Luca Mechelli
Monica Sforna
author_facet Chiara Brachelente
Katia Cappelli
Stefano Capomaccio
Ilaria Porcellato
Serenella Silvestri
Laura Bongiovanni
Raffaella De Maria
Andrea Verini Supplizi
Luca Mechelli
Monica Sforna
author_sort Chiara Brachelente
title Transcriptome Analysis of Canine Cutaneous Melanoma and Melanocytoma Reveals a Modulation of Genes Regulating Extracellular Matrix Metabolism and Cell Cycle
title_short Transcriptome Analysis of Canine Cutaneous Melanoma and Melanocytoma Reveals a Modulation of Genes Regulating Extracellular Matrix Metabolism and Cell Cycle
title_full Transcriptome Analysis of Canine Cutaneous Melanoma and Melanocytoma Reveals a Modulation of Genes Regulating Extracellular Matrix Metabolism and Cell Cycle
title_fullStr Transcriptome Analysis of Canine Cutaneous Melanoma and Melanocytoma Reveals a Modulation of Genes Regulating Extracellular Matrix Metabolism and Cell Cycle
title_full_unstemmed Transcriptome Analysis of Canine Cutaneous Melanoma and Melanocytoma Reveals a Modulation of Genes Regulating Extracellular Matrix Metabolism and Cell Cycle
title_sort transcriptome analysis of canine cutaneous melanoma and melanocytoma reveals a modulation of genes regulating extracellular matrix metabolism and cell cycle
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/4d21a72599b74ab18450ea884c9a4555
work_keys_str_mv AT chiarabrachelente transcriptomeanalysisofcaninecutaneousmelanomaandmelanocytomarevealsamodulationofgenesregulatingextracellularmatrixmetabolismandcellcycle
AT katiacappelli transcriptomeanalysisofcaninecutaneousmelanomaandmelanocytomarevealsamodulationofgenesregulatingextracellularmatrixmetabolismandcellcycle
AT stefanocapomaccio transcriptomeanalysisofcaninecutaneousmelanomaandmelanocytomarevealsamodulationofgenesregulatingextracellularmatrixmetabolismandcellcycle
AT ilariaporcellato transcriptomeanalysisofcaninecutaneousmelanomaandmelanocytomarevealsamodulationofgenesregulatingextracellularmatrixmetabolismandcellcycle
AT serenellasilvestri transcriptomeanalysisofcaninecutaneousmelanomaandmelanocytomarevealsamodulationofgenesregulatingextracellularmatrixmetabolismandcellcycle
AT laurabongiovanni transcriptomeanalysisofcaninecutaneousmelanomaandmelanocytomarevealsamodulationofgenesregulatingextracellularmatrixmetabolismandcellcycle
AT raffaellademaria transcriptomeanalysisofcaninecutaneousmelanomaandmelanocytomarevealsamodulationofgenesregulatingextracellularmatrixmetabolismandcellcycle
AT andreaverinisupplizi transcriptomeanalysisofcaninecutaneousmelanomaandmelanocytomarevealsamodulationofgenesregulatingextracellularmatrixmetabolismandcellcycle
AT lucamechelli transcriptomeanalysisofcaninecutaneousmelanomaandmelanocytomarevealsamodulationofgenesregulatingextracellularmatrixmetabolismandcellcycle
AT monicasforna transcriptomeanalysisofcaninecutaneousmelanomaandmelanocytomarevealsamodulationofgenesregulatingextracellularmatrixmetabolismandcellcycle
_version_ 1718393916376481792