Hypoxia-induced adaptations of mirnomes and proteomes in melanoma cells and their secreted extracellular vesicles

Geoffroy Walbrecq, Odile Lecha, Anthoula Gaigneaux, Miriam R. Fougeras, Demetra Philippidou, Christiane Margue, Milène Tetsi Nomigni, François Bernardin, Gunnar Dittmar, Iris Behrmann, Stephanie Kreis*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

22 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number692
JournalCancers
Volume12
Issue number3
DOIs
Publication statusPublished - Mar 2020

Keywords

  • Extracellular vesicles
  • Hypoxia
  • Melanoma
  • MiRNome
  • Proteome

Fingerprint

Dive into the research topics of 'Hypoxia-induced adaptations of mirnomes and proteomes in melanoma cells and their secreted extracellular vesicles'. Together they form a unique fingerprint.

Cite this