TY - JOUR
T1 - Hypoxia-induced adaptations of mirnomes and proteomes in melanoma cells and their secreted extracellular vesicles
AU - Walbrecq, Geoffroy
AU - Lecha, Odile
AU - Gaigneaux, Anthoula
AU - Fougeras, Miriam R.
AU - Philippidou, Demetra
AU - Margue, Christiane
AU - Nomigni, Milène Tetsi
AU - Bernardin, François
AU - Dittmar, Gunnar
AU - Behrmann, Iris
AU - Kreis, Stephanie
N1 - Funding Information:
Funding: The study was supported by a grant from the Fondation Cancer, Luxembourg (SecMelPro grant). O.L. was financed by the Fondation Cancer, Luxembourg. M.R.F. was supported by the CanBio DTU (PRIDE15/10675146/CANBIO) of the Fonds National de la Recherche (FNR), Luxembourg.
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/3
Y1 - 2020/3
N2 - 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 IPO11 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.
AB - 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 IPO11 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.
KW - Extracellular vesicles
KW - Hypoxia
KW - Melanoma
KW - MiRNome
KW - Proteome
UR - http://www.scopus.com/inward/record.url?scp=85082494633&partnerID=8YFLogxK
UR - https://pubmed.ncbi.nlm.nih.gov/32183388
U2 - 10.3390/cancers12030692
DO - 10.3390/cancers12030692
M3 - Article
C2 - 32183388
AN - SCOPUS:85082494633
SN - 2072-6694
VL - 12
JO - Cancers
JF - Cancers
IS - 3
M1 - 692
ER -