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.

Publication Title

Clin Epigenetics

Authors

Cécile Desjobert
Arnaud Carrier
Audrey Delmas
Diego M Marzese, Department of Translational Molecular Medicine, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CAFollow
Antoine Daunay
Florence Busato
Arnaud Pillon
Jörg Tost
Joëlle Riond
Gilles Favre
Chantal Etievant
Paola B Arimondo

Document Type

Article

Publication Date

1-16-2019

Keywords

DNA methylation; Epigenetics; Melanoma aggressiveness; microRNA

Abstract

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.

Area of Special Interest

Cancer

Specialty/Research Institute

Oncology