miR-200c-driven Mesenchymal-To-Epithelial Transition is a Therapeutic Target in Uterine Carcinosarcomas

Abstract Uterine carcinosarcomas (UCSs) are highly aggressive malignancies associated with poor prognoses and limited treatment options. These tumors are hypothesized to develop from the endometrial adenocarcinoma (EAC) through epithelial-mesenchymal transition (EMT). We test this long-standing hypo...

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Autores principales:	Jill H. Tseng, Maria Bisogna, Lien N. Hoang, Narciso Olvera, Cristian Rodriguez-Aguayo, Gabriel Lopez-Berestein, Anil K. Sood, Douglas A. Levine, Petar Jelinic
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/39afe2c454444995b3b4910c761be8ac
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spelling	oai:doaj.org-article:39afe2c454444995b3b4910c761be8ac2021-12-02T12:32:05ZmiR-200c-driven Mesenchymal-To-Epithelial Transition is a Therapeutic Target in Uterine Carcinosarcomas10.1038/s41598-017-03972-72045-2322https://doaj.org/article/39afe2c454444995b3b4910c761be8ac2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03972-7https://doaj.org/toc/2045-2322Abstract Uterine carcinosarcomas (UCSs) are highly aggressive malignancies associated with poor prognoses and limited treatment options. These tumors are hypothesized to develop from the endometrial adenocarcinoma (EAC) through epithelial-mesenchymal transition (EMT). We test this long-standing hypothesis by depleting miR-200, a family of microRNAs critical for EMT, in EAC cell lines. Our data suggest that UCSs do not develop from EACs via EMT. Clinically more relevant, we show that miR-200 expression in UCS cells induces a robust mesenchymal-epithelial transition (MET). Using in vitro and murine xenograft models, we demonstrate decreased growth and aggressiveness of miR-200-overexpressing UCS cell lines. Whole transcriptome analysis confirmed changes consistent with an MET and also revealed changes in angiogenic genes expression. Finally, by treatment of UCS-xenografted mice with miR-200c incorporated in DOPC nanoliposomes, we demonstrate anti-tumor activities. These findings suggest that ectopic miR-200 expression using advanced microRNA therapeutics may be a potential treatment approach for patients with UCS.Jill H. TsengMaria BisognaLien N. HoangNarciso OlveraCristian Rodriguez-AguayoGabriel Lopez-BeresteinAnil K. SoodDouglas A. LevinePetar JelinicNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jill H. Tseng Maria Bisogna Lien N. Hoang Narciso Olvera Cristian Rodriguez-Aguayo Gabriel Lopez-Berestein Anil K. Sood Douglas A. Levine Petar Jelinic miR-200c-driven Mesenchymal-To-Epithelial Transition is a Therapeutic Target in Uterine Carcinosarcomas
description	Abstract Uterine carcinosarcomas (UCSs) are highly aggressive malignancies associated with poor prognoses and limited treatment options. These tumors are hypothesized to develop from the endometrial adenocarcinoma (EAC) through epithelial-mesenchymal transition (EMT). We test this long-standing hypothesis by depleting miR-200, a family of microRNAs critical for EMT, in EAC cell lines. Our data suggest that UCSs do not develop from EACs via EMT. Clinically more relevant, we show that miR-200 expression in UCS cells induces a robust mesenchymal-epithelial transition (MET). Using in vitro and murine xenograft models, we demonstrate decreased growth and aggressiveness of miR-200-overexpressing UCS cell lines. Whole transcriptome analysis confirmed changes consistent with an MET and also revealed changes in angiogenic genes expression. Finally, by treatment of UCS-xenografted mice with miR-200c incorporated in DOPC nanoliposomes, we demonstrate anti-tumor activities. These findings suggest that ectopic miR-200 expression using advanced microRNA therapeutics may be a potential treatment approach for patients with UCS.
format	article
author	Jill H. Tseng Maria Bisogna Lien N. Hoang Narciso Olvera Cristian Rodriguez-Aguayo Gabriel Lopez-Berestein Anil K. Sood Douglas A. Levine Petar Jelinic
author_facet	Jill H. Tseng Maria Bisogna Lien N. Hoang Narciso Olvera Cristian Rodriguez-Aguayo Gabriel Lopez-Berestein Anil K. Sood Douglas A. Levine Petar Jelinic
author_sort	Jill H. Tseng
title	miR-200c-driven Mesenchymal-To-Epithelial Transition is a Therapeutic Target in Uterine Carcinosarcomas
title_short	miR-200c-driven Mesenchymal-To-Epithelial Transition is a Therapeutic Target in Uterine Carcinosarcomas
title_full	miR-200c-driven Mesenchymal-To-Epithelial Transition is a Therapeutic Target in Uterine Carcinosarcomas
title_fullStr	miR-200c-driven Mesenchymal-To-Epithelial Transition is a Therapeutic Target in Uterine Carcinosarcomas
title_full_unstemmed	miR-200c-driven Mesenchymal-To-Epithelial Transition is a Therapeutic Target in Uterine Carcinosarcomas
title_sort	mir-200c-driven mesenchymal-to-epithelial transition is a therapeutic target in uterine carcinosarcomas
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/39afe2c454444995b3b4910c761be8ac
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miR-200c-driven Mesenchymal-To-Epithelial Transition is a Therapeutic Target in Uterine Carcinosarcomas

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