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Exosome-Mediated Paracrine Signaling Unveils miR-1246 as a Driver of Aggressiveness in Fusion-Negative Rhabdomyosarcoma.
Ramadan, Farah; Saab, Raya; Ghamloush, Farah; Khoueiry, Rita; Herceg, Zdenko; Gomez, Ludovic; Badran, Bassam; Clezardin, Philippe; Hussein, Nader; Cohen, Pascale A; Ghayad, Sandra E.
Afiliação
  • Ramadan F; Université Lyon 1, Lyon, France.
  • Saab R; INSERM, Research Unit UMR_S1033, LyOS, Faculty of Medicine Lyon-Est, 69372 Lyon, France.
  • Ghamloush F; Department of Biology, Faculty of Science II, Lebanese University, Beirut 6573, Lebanon.
  • Khoueiry R; Laboratory of Cancer Biology and Molecular Immunology, Department of Chemistry and Biochemistry, Faculty of Science I, Lebanese University, Hadath 1103, Lebanon.
  • Herceg Z; Department of Pediatrics & Adolescent Medicine, American University of Beirut Medical Center, Beirut 1107, Lebanon.
  • Gomez L; Department of Anatomy, Cell Biology and Physiology, Faculty of Medicine, American University of Beirut, Beirut 1107, Lebanon.
  • Badran B; Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
  • Clezardin P; Department of Pediatrics & Adolescent Medicine, American University of Beirut Medical Center, Beirut 1107, Lebanon.
  • Hussein N; Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, World Health Organization, 69366 Cedex 07 Lyon, France.
  • Cohen PA; Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, World Health Organization, 69366 Cedex 07 Lyon, France.
  • Ghayad SE; Laboratoire CarMeN-IRIS Team, INSERM, INRA, Université Claude Bernard Lyon-1, INSA-Lyon, Univ-Lyon, 69500 Bron, France.
Cancers (Basel) ; 16(9)2024 Apr 25.
Article em En | MEDLINE | ID: mdl-38730605
ABSTRACT
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 GSK3ß and promotes ß-catenin nuclear accumulation, suggesting a deregulation of the Wnt pathway, known to be important in tumor progression. Finally, a pilot clinical study highlighted, for the first time, the presence of high exosomal miR-1246 levels in RMS patients' sera. Altogether, our results demonstrate that exosomal miR-1246 has the potential to alter the tumor microenvironment of FN-RMS cells, suggesting its potential role in promoting oncogenesis.
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Texto completo: 1 Bases de dados: MEDLINE Idioma: En Revista: Cancers (Basel) Ano de publicação: 2024 Tipo de documento: Article País de afiliação: França

Texto completo: 1 Bases de dados: MEDLINE Idioma: En Revista: Cancers (Basel) Ano de publicação: 2024 Tipo de documento: Article País de afiliação: França