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© Research
Publication : Clinical epigenetics

Demethylation by low-dose 5-aza-2′-deoxycytidine impairs 3D melanoma invasion partially through miR-199a-3p expression revealing the role of this miR in melanoma

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Clinical epigenetics - 16 Jan 2019

Desjobert C, Carrier A, Delmas A, Marzese DM, Daunay A, Busato F, Pillon A, Tost J, Riond J, Favre G, Etievant C, Arimondo PB

Link to Pubmed [PMID] – 30651148

Clin Epigenetics 2019 Jan;11(1):9

BACKGROUND: Efficient treatments against metastatic melanoma dissemination are still lacking. Here, we report that low-cytotoxic concentrations of 5-aza-2′-deoxycytidine, a DNA demethylating agent, prevent in vitro 3D invasiveness of metastatic melanoma cells and reduce lung metastasis formation in vivo.

RESULTS: We unravelled that this beneficial effect is in part due to MIR-199A2 re-expression by promoter demethylation. Alone, this miR showed an anti-invasive and anti-metastatic effect. Throughout integration of micro-RNA target prediction databases with transcriptomic analysis after 5-aza-2′-deoxycytidine treatments, we found that miR-199a-3p downregulates set of genes significantly involved in invasion/migration processes. In addition, analysis of data from melanoma patients showed a stage- and tissue type-dependent modulation of MIR-199A2 expression by DNA methylation.

CONCLUSIONS: Thus, our data suggest that epigenetic- and/or miR-based therapeutic strategies can be relevant to limit metastatic dissemination of melanoma.

https://www.ncbi.nlm.nih.gov/pubmed/30651148