Hypoxia-Induced Adaptations of miRNomes and Proteomes in Melanoma Cells and Their Secreted Extracellular Vesicles
Reduced levels of intratumoural oxygen are associated with hypoxia-induced pro-oncogenic events such as invasion, metabolic reprogramming, epithelial−mesenchymal transition, metastasis and resistance to therapy, all favouring cancer progression. Small extracellular vesicles (EV) shuttle va...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-03-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/3/692 |
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| author | Geoffroy Walbrecq Odile Lecha Anthoula Gaigneaux Miriam R. Fougeras Demetra Philippidou Christiane Margue Milène Tetsi Nomigni François Bernardin Gunnar Dittmar Iris Behrmann Stephanie Kreis |
| author_facet | Geoffroy Walbrecq Odile Lecha Anthoula Gaigneaux Miriam R. Fougeras Demetra Philippidou Christiane Margue Milène Tetsi Nomigni François Bernardin Gunnar Dittmar Iris Behrmann Stephanie Kreis |
| author_sort | Geoffroy Walbrecq |
| collection | DOAJ |
| description | Reduced levels of intratumoural oxygen are associated with hypoxia-induced pro-oncogenic events such as invasion, metabolic reprogramming, epithelial−mesenchymal transition, metastasis and resistance to therapy, all favouring cancer progression. Small extracellular vesicles (EV) shuttle various cargos (proteins, miRNAs, DNA and others). Tumour-derived EVs can be taken up by neighbouring or distant cells in the tumour microenvironment, thus facilitating intercellular communication. The quantity of extracellular vesicle secretion and their composition can vary with changing microenvironmental conditions and disease states. Here, we investigated in melanoma cells the influence of hypoxia on the content and number of secreted EVs. Whole miRNome and proteome profiling revealed distinct expression patterns in normoxic or hypoxic growth conditions. Apart from the well-known miR-210, we identified miR-1290 as a novel hypoxia-associated microRNA, which was highly abundant in hypoxic EVs. On the other hand, miR-23a-5p and -23b-5p were consistently downregulated in hypoxic conditions, while the protein levels of the miR-23a/b-5p-predicted target <i>IPO11</i> were concomitantly upregulated. Furthermore, hypoxic melanoma EVs exhibit a signature consisting of six proteins (AKR7A2, DDX39B, EIF3C, FARSA, PRMT5, VARS), which were significantly associated with a poor prognosis for melanoma patients, indicating that proteins and/or miRNAs secreted by cancer cells may be exploited as biomarkers. |
| first_indexed | 2024-03-12T19:39:15Z |
| format | Article |
| id | doaj.art-47dc2ddeb4784041982f0cb6bc5b5b76 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T19:39:15Z |
| publishDate | 2020-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-47dc2ddeb4784041982f0cb6bc5b5b762023-08-02T03:55:41ZengMDPI AGCancers2072-66942020-03-0112369210.3390/cancers12030692cancers12030692Hypoxia-Induced Adaptations of miRNomes and Proteomes in Melanoma Cells and Their Secreted Extracellular VesiclesGeoffroy Walbrecq0Odile Lecha1Anthoula Gaigneaux2Miriam R. Fougeras3Demetra Philippidou4Christiane Margue5Milène Tetsi Nomigni6François Bernardin7Gunnar Dittmar8Iris Behrmann9Stephanie Kreis10Department of Life Sciences and Medicine, University of Luxembourg, 6, avenue du Swing, L-4367 Belvaux, LuxembourgDepartment of Life Sciences and Medicine, University of Luxembourg, 6, avenue du Swing, L-4367 Belvaux, LuxembourgDepartment of Life Sciences and Medicine, University of Luxembourg, 6, avenue du Swing, L-4367 Belvaux, LuxembourgProteomics of Cellular Signaling, Quantitative Biology Unit, Luxembourg Institute of Health, 1A-B, rue Thomas Edison, L-1445 Strassen, LuxembourgDepartment of Life Sciences and Medicine, University of Luxembourg, 6, avenue du Swing, L-4367 Belvaux, LuxembourgDepartment of Life Sciences and Medicine, University of Luxembourg, 6, avenue du Swing, L-4367 Belvaux, LuxembourgDepartment of Life Sciences and Medicine, University of Luxembourg, 6, avenue du Swing, L-4367 Belvaux, LuxembourgProteomics of Cellular Signaling, Quantitative Biology Unit, Luxembourg Institute of Health, 1A-B, rue Thomas Edison, L-1445 Strassen, LuxembourgDepartment of Life Sciences and Medicine, University of Luxembourg, 6, avenue du Swing, L-4367 Belvaux, LuxembourgDepartment of Life Sciences and Medicine, University of Luxembourg, 6, avenue du Swing, L-4367 Belvaux, LuxembourgDepartment of Life Sciences and Medicine, University of Luxembourg, 6, avenue du Swing, L-4367 Belvaux, LuxembourgReduced levels of intratumoural oxygen are associated with hypoxia-induced pro-oncogenic events such as invasion, metabolic reprogramming, epithelial−mesenchymal transition, metastasis and resistance to therapy, all favouring cancer progression. Small extracellular vesicles (EV) shuttle various cargos (proteins, miRNAs, DNA and others). Tumour-derived EVs can be taken up by neighbouring or distant cells in the tumour microenvironment, thus facilitating intercellular communication. The quantity of extracellular vesicle secretion and their composition can vary with changing microenvironmental conditions and disease states. Here, we investigated in melanoma cells the influence of hypoxia on the content and number of secreted EVs. Whole miRNome and proteome profiling revealed distinct expression patterns in normoxic or hypoxic growth conditions. Apart from the well-known miR-210, we identified miR-1290 as a novel hypoxia-associated microRNA, which was highly abundant in hypoxic EVs. On the other hand, miR-23a-5p and -23b-5p were consistently downregulated in hypoxic conditions, while the protein levels of the miR-23a/b-5p-predicted target <i>IPO11</i> were concomitantly upregulated. Furthermore, hypoxic melanoma EVs exhibit a signature consisting of six proteins (AKR7A2, DDX39B, EIF3C, FARSA, PRMT5, VARS), which were significantly associated with a poor prognosis for melanoma patients, indicating that proteins and/or miRNAs secreted by cancer cells may be exploited as biomarkers.https://www.mdpi.com/2072-6694/12/3/692melanomahypoxiaextracellular vesiclesproteomemirnome |
| spellingShingle | Geoffroy Walbrecq Odile Lecha Anthoula Gaigneaux Miriam R. Fougeras Demetra Philippidou Christiane Margue Milène Tetsi Nomigni François Bernardin Gunnar Dittmar Iris Behrmann Stephanie Kreis Hypoxia-Induced Adaptations of miRNomes and Proteomes in Melanoma Cells and Their Secreted Extracellular Vesicles Cancers melanoma hypoxia extracellular vesicles proteome mirnome |
| title | Hypoxia-Induced Adaptations of miRNomes and Proteomes in Melanoma Cells and Their Secreted Extracellular Vesicles |
| title_full | Hypoxia-Induced Adaptations of miRNomes and Proteomes in Melanoma Cells and Their Secreted Extracellular Vesicles |
| title_fullStr | Hypoxia-Induced Adaptations of miRNomes and Proteomes in Melanoma Cells and Their Secreted Extracellular Vesicles |
| title_full_unstemmed | Hypoxia-Induced Adaptations of miRNomes and Proteomes in Melanoma Cells and Their Secreted Extracellular Vesicles |
| title_short | Hypoxia-Induced Adaptations of miRNomes and Proteomes in Melanoma Cells and Their Secreted Extracellular Vesicles |
| title_sort | hypoxia induced adaptations of mirnomes and proteomes in melanoma cells and their secreted extracellular vesicles |
| topic | melanoma hypoxia extracellular vesicles proteome mirnome |
| url | https://www.mdpi.com/2072-6694/12/3/692 |
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