The PAX3-FOXO1 oncogene alters exosome miRNA content and leads to paracrine effects mediated by exosomal miR-486

Abstract Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. The alveolar subtype (ARMS) is clinically more aggressive, and characterized by an oncogenic fusion protein PAX3-FOXO1 that drives oncogenic cellular properties. Exosomes are small, secreted vesicles that affect para...

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Autores principales:	Farah Ghamloush, Sandra E. Ghayad, Ghina Rammal, Assil Fahs, Abeer J. Ayoub, Zeina Merabi, Mohamad Harajly, Hassan Zalzali, Raya Saab
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/48ff41dea4bf4d4aae9196741925086f
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spelling	oai:doaj.org-article:48ff41dea4bf4d4aae9196741925086f2021-12-02T15:09:28ZThe PAX3-FOXO1 oncogene alters exosome miRNA content and leads to paracrine effects mediated by exosomal miR-48610.1038/s41598-019-50592-42045-2322https://doaj.org/article/48ff41dea4bf4d4aae9196741925086f2019-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-50592-4https://doaj.org/toc/2045-2322Abstract Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. The alveolar subtype (ARMS) is clinically more aggressive, and characterized by an oncogenic fusion protein PAX3-FOXO1 that drives oncogenic cellular properties. Exosomes are small, secreted vesicles that affect paracrine signaling. We show that PAX3-FOXO1 transcript alters exosome content of C2C12 myoblasts, leading to pro-tumorigenic paracrine effects in recipient cells. Microarray analysis revealed alteration in miRNA content of exosomes, affecting cellular networks involved in cell metabolism, growth signaling, and cellular invasion. Overexpression and knockdown studies showed that miR-486-5p is an effector of PAX3-FOXO1, and mediates its paracrine effects in exosomes, including promoting recipient cell migration, invasion, and colony formation. Analysis of human RMS cells showed miR-486-5p is enriched in both cells and exosomes, and to a higher extent in ARMS subtypes. Analysis of human serum samples showed that miR-486-5p is enriched in exosomes of patients with RMS, and follow-up after chemotherapy showed decrease to control values. Our findings identify a novel role of both PAX3-FOXO1 and its downstream effector miR-486-5p in exosome-mediated oncogenic paracrine effects of RMS, and suggest its possible use as a biomarker.Farah GhamloushSandra E. GhayadGhina RammalAssil FahsAbeer J. AyoubZeina MerabiMohamad HarajlyHassan ZalzaliRaya SaabNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-12 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Farah Ghamloush Sandra E. Ghayad Ghina Rammal Assil Fahs Abeer J. Ayoub Zeina Merabi Mohamad Harajly Hassan Zalzali Raya Saab The PAX3-FOXO1 oncogene alters exosome miRNA content and leads to paracrine effects mediated by exosomal miR-486
description	Abstract Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. The alveolar subtype (ARMS) is clinically more aggressive, and characterized by an oncogenic fusion protein PAX3-FOXO1 that drives oncogenic cellular properties. Exosomes are small, secreted vesicles that affect paracrine signaling. We show that PAX3-FOXO1 transcript alters exosome content of C2C12 myoblasts, leading to pro-tumorigenic paracrine effects in recipient cells. Microarray analysis revealed alteration in miRNA content of exosomes, affecting cellular networks involved in cell metabolism, growth signaling, and cellular invasion. Overexpression and knockdown studies showed that miR-486-5p is an effector of PAX3-FOXO1, and mediates its paracrine effects in exosomes, including promoting recipient cell migration, invasion, and colony formation. Analysis of human RMS cells showed miR-486-5p is enriched in both cells and exosomes, and to a higher extent in ARMS subtypes. Analysis of human serum samples showed that miR-486-5p is enriched in exosomes of patients with RMS, and follow-up after chemotherapy showed decrease to control values. Our findings identify a novel role of both PAX3-FOXO1 and its downstream effector miR-486-5p in exosome-mediated oncogenic paracrine effects of RMS, and suggest its possible use as a biomarker.
format	article
author	Farah Ghamloush Sandra E. Ghayad Ghina Rammal Assil Fahs Abeer J. Ayoub Zeina Merabi Mohamad Harajly Hassan Zalzali Raya Saab
author_facet	Farah Ghamloush Sandra E. Ghayad Ghina Rammal Assil Fahs Abeer J. Ayoub Zeina Merabi Mohamad Harajly Hassan Zalzali Raya Saab
author_sort	Farah Ghamloush
title	The PAX3-FOXO1 oncogene alters exosome miRNA content and leads to paracrine effects mediated by exosomal miR-486
title_short	The PAX3-FOXO1 oncogene alters exosome miRNA content and leads to paracrine effects mediated by exosomal miR-486
title_full	The PAX3-FOXO1 oncogene alters exosome miRNA content and leads to paracrine effects mediated by exosomal miR-486
title_fullStr	The PAX3-FOXO1 oncogene alters exosome miRNA content and leads to paracrine effects mediated by exosomal miR-486
title_full_unstemmed	The PAX3-FOXO1 oncogene alters exosome miRNA content and leads to paracrine effects mediated by exosomal miR-486
title_sort	pax3-foxo1 oncogene alters exosome mirna content and leads to paracrine effects mediated by exosomal mir-486
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/48ff41dea4bf4d4aae9196741925086f
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The PAX3-FOXO1 oncogene alters exosome miRNA content and leads to paracrine effects mediated by exosomal miR-486

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