Transcriptome Analysis of Canine Cutaneous Melanoma and Melanocytoma Reveals a Modulation of Genes Regulating Extracellular Matrix Metabolism and Cell Cycle
Autor: | Laura Bongiovanni, Luca Mechelli, Monica Sforna, Chiara Brachelente, Raffaella De Maria, Ilaria Porcellato, Katia Cappelli, Serenella Silvestri, Andrea Verini Supplizi, Stefano Capomaccio |
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Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Male canine melanoma RNA seq molecula pathway Skin Neoplasms Protein digestion Science Biology Skin Diseases Article Transcriptome Extracellular matrix 03 medical and health sciences Animals Cell Cycle Collagen Dog Diseases Dogs Extracellular Matrix Female Gene Expression Profiling Gene Expression Regulation Neoplastic Melanoma Sequence Analysis RNA Gene Regulatory Networks Multidisciplinary RNA seq Canine Melanoma medicine melanoma RNA-Seq canine melanoma Tumor microenvironment Neoplastic molecula pathway melanoma dog RNA-Seq medicine.disease 030104 developmental biology Gene Expression Regulation Cutaneous melanoma dog Cancer research RNA Medicine Melanocytoma Sequence Analysis |
Zdroj: | Scientific Reports, Vol 7, Iss 1, Pp 1-12 (2017) Scientific Reports |
ISSN: | 2045-2322 |
Popis: | 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. |
Databáze: | OpenAIRE |
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