[en] 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 targetIPO11were 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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Walbrecq, Geoffroy; University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Lecha, Odile; University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
GAIGNEAUX, Anthoula ; University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Fougeras, Miriam R .; Luxembourg Institute of Health > Proteomics of Cellular Signaling, Quantitative Biology Unit
PHILIPPIDOU, Demetra ; University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
MARGUE, Christiane ; University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
TETSI NOMIGNI, Milène ; University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Bernardin, François; Luxembourg Institute of Health > Proteomics of Cellular Signaling, Quantitative Biology Unit
DITTMAR, Gunnar ; University of Luxembourg > Faculty of Science, Technology and Communication (FSTC)
BEHRMANN, Iris ; University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
KREIS, Stephanie ; University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
External co-authors :
no
Language :
English
Title :
Hypoxia-Induced Adaptations of miRNomes and Proteomes in Melanoma Cells and Their Secreted Extracellular Vesicles