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MicroRNAs in adrenocortical cancer : function and clinical potential

Mardi 21 février 2017 11:00 - Duree : 1 heure
Lieu : Salle de Conférence de l’IAB - Rond Point de La Chantourne, 38700 La Tronche (arrêt de tram Grand Sablon, ligne B)

Orateur : Nadia CHERRADI (CEA, Grenoble)

Adrenocortical carcinoma (ACC) is a rare but highly aggressive malignancy with poor prognosis and limited therapeutic options. Over the last few years, integration of gene expression profile data with exome sequencing, SNP array analysis, methylation and microRNA (miRNA) profiling led to the identification of subgroups of malignant tumors with distinct molecular alterations and clinical outcomes. Despite these major advances, our understanding of the contribution of miRNAs to the pathogenesis of ACC is still in its infancy. We have identified tumor as well as serum microRNA signatures that carry potential diagnostic and prognostic values. Among overexpressed circulating microRNAs in ACC patients, miR-139-5p and miR-483-5p appeared as promising non-invasive biomarkers of malignancy or recurrence, respectively. Moreover, using integrated analyses combining transcriptomic and miRnomic data, we demonstrated that miR-483-5p and miR-139-5p targeted two members of the N-Myc Downstream Regulated Gene family and play a yet unrecognized role in adrenocortical cancer aggressiveness. Finally, in light of recent insights into the role of extracellular miRNAs in shaping the tumor microenvironment, we are currently studying the impact of adrenocortical cancer cell-derived miR-483-5p and miR-139-5p on endothelial cell (EC) function. Both cancer cell-derived miR-483-5p and miR-139- 5p were found to be released within exosomes and were taken up by recipient EC. Our preliminary data suggest an angiogenic role of exosomes and exosomal miR-483-5p and miR-139-5p, which highlights their potential for applications in miRNA-based therapeutics for ACC with poor outcome.

Contact : karin.sadoul@univ-grenoble-alpes.fr

Discipline évènement : (Biologie / Chimie)
Entité organisatrice : (IAB)
Nature évènement : (Séminaire)
Evènement répétitif : (Mardis de l’IAB)
Site de l'évènement : Pôle Santé / La Tronche

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