Cancers, Vol. 16, Pages 1652: Exosome-Mediated Paracrine Signaling Unveils miR-1246 as a Driver of Aggressiveness in Fusion-Negative Rhabdomyosarcoma

Cancers, Vol. 16, Pages 1652: Exosome-Mediated Paracrine Signaling Unveils miR-1246 as a Driver of Aggressiveness in Fusion-Negative Rhabdomyosarcoma Cancers doi: 10.3390/cancers16091652 Authors: Farah Ramadan Raya Saab Farah Ghamloush Rita Khoueiry Zdenko Herceg Ludovic Gomez Bassam Badran Philippe Clezardin Nader Hussein Pascale A. Cohen Sandra E. Ghayad Rhabdomyosarcoma is a pediatric cancer associated with aggressiveness and a tendency to develop metastases. Fusion-negative rhabdomyosarcoma (FN-RMS) is the most commonly occurring subtype of RMS, where metastatic disease can hinder treatment success and decrease survival rates. RMS-derived exosomes were previously demonstrated to be enriched with miRNAs, including miR-1246, possibly contributing to disease aggressiveness. We aimed to decipher the functional impact of exosomal miR-1246 on recipient cells and its role in promoting aggressiveness. Treatment of normal fibroblasts with FN-RMS-derived exosomes resulted in a significant uptake of miR-1246 paired with an increase in cell proliferation, migration, and invasion. In turn, delivery of miR-1246-mimic lipoplexes promoted fibroblast proliferation, migration, and invasion in a similar manner. Conversely, when silencing miR-1246 in FN-RMS cells, the resulting derived exosomes demonstrated reversed effects on recipient cells’ phenotype. Delivery of exosomal miR-1246 targets GSK3β and promotes β-catenin nucl...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research