Journal
NUCLEIC ACIDS RESEARCH
Volume 45, Issue 7, Pages 4131-4141Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkw1284
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Funding
- French Government (Agence Nationale de Recherche, ANR) through the 'Investments for the Future' LABEX SIGNALIFE [ANR-11-LABX-0028-01]
- ANR Jeunes Chercheurs Jeunes Chercheuses [ANR-12-JSV1-0009-01]
- Infrastructure France-Genomique [ANR-10-INBS-09-03]
- Fondation ARC pour la recherche sur le cancer [ARC SL220110603478]
- CANC'AIR Genexposomic project, Canceropole PACA
- Region PACA (France)
- Conseil General [06]
- FEDER
- Ministere de l'Enseignement Superieur
- Region Provence Alpes-Cote d'Azur
- INSERM
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Extracellular vesicles (EVs) have been shown to play an important role in intercellular communication as carriers of DNA, RNA and proteins. While the intercellular transfer of miRNA through EVs has been extensively studied, the stability of extracellular miRNA (ex-miRNA) once engulfed by a recipient cell remains to be determined. Here, we identify the ex-miRNA-directed phenotype to be transient due to the rapid decay of ex-miRNA. We demonstrate that the ex-miR-223-3p transferred from polymorphonuclear leukocytes to cancer cells were functional, as demonstrated by the decreased expression of its target FOXO1 and the occurrence of epithelial-mesenchymal transition reprogramming. We showed that the engulfed ex-miRNA, unlike endogenous miRNA, was unstable, enabling dynamic regulation and a return to a non-invasive phenotype within 8 h. This transient phenotype could be modulated by targeting XRN1/PACMAN exonuclease. Indeed, its silencing was associated with slower decay of exmiR-223-3p and subsequently prolonged the invasive properties. In conclusion, we showed that the 'steady step' level of engulfed miRNA and its subsequent activity was dependent on the presence of a donor cell in the surroundings to constantly fuel the recipient cellwith ex-miRNAs and of XRN1 exonuclease, which is involved in the decay of these imported miRNA.
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