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

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...

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Published in:Scientific reports 2017-06, Vol.7 (1), p.3614-13, Article 3614
Main Authors: Tseng, Jill H., Bisogna, Maria, Hoang, Lien N., Olvera, Narciso, Rodriguez-Aguayo, Cristian, Lopez-Berestein, Gabriel, Sood, Anil K., Levine, Douglas A., Jelinic, Petar
Format: Article
Language:English
Subjects:
13/51
38/39
45/90
631/337/384/331
631/67/1517/1931
64/60
82/80
96/106
96/109
Adenocarcinoma
Angiogenesis
Animal models
Animals
Antitumor agents
Cancer therapies
Carcinosarcoma - genetics
Carcinosarcoma - pathology
Cell Adhesion
Cell Movement
Cell Proliferation
Cell Survival
Chemotherapy
Chromosomes
Cloning
Computational Biology - methods
Disease Models, Animal
Endometrium
Epithelial-Mesenchymal Transition - genetics
Female
Gene expression
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Genotype & phenotype
Humanities and Social Sciences
Humans
Hypotheses
Medical prognosis
Mesenchyme
Mice
MicroRNAs
MicroRNAs - genetics
miRNA
multidisciplinary
Mutation
Neovascularization, Pathologic - genetics
Prognosis
Science
Science (multidisciplinary)
Therapeutic applications
Tumors
Uterine Neoplasms - genetics
Uterine Neoplasms - pathology
Uterus
Xenograft Model Antitumor Assays
Xenografts
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cited_by cdi_FETCH-LOGICAL-c606t-47fd58455741c854c2c15bbaccbfb2a82d653dde3058963e84a559fbcc656b073
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creator Tseng, Jill H.
Bisogna, Maria
Hoang, Lien N.
Olvera, Narciso
Rodriguez-Aguayo, Cristian
Lopez-Berestein, Gabriel
Sood, Anil K.
Levine, Douglas A.
Jelinic, Petar
description 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.
doi_str_mv 10.1038/s41598-017-03972-7
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Bisogna, Maria ; Hoang, Lien N. ; Olvera, Narciso ; Rodriguez-Aguayo, Cristian ; Lopez-Berestein, Gabriel ; Sood, Anil K. ; Levine, Douglas A. ; Jelinic, Petar</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c606t-47fd58455741c854c2c15bbaccbfb2a82d653dde3058963e84a559fbcc656b073</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>13/51</topic><topic>38/39</topic><topic>45/90</topic><topic>631/337/384/331</topic><topic>631/67/1517/1931</topic><topic>64/60</topic><topic>82/80</topic><topic>96/106</topic><topic>96/109</topic><topic>Adenocarcinoma</topic><topic>Angiogenesis</topic><topic>Animal models</topic><topic>Animals</topic><topic>Antitumor agents</topic><topic>Cancer therapies</topic><topic>Carcinosarcoma - genetics</topic><topic>Carcinosarcoma - pathology</topic><topic>Cell Adhesion</topic><topic>Cell Movement</topic><topic>Cell Proliferation</topic><topic>Cell Survival</topic><topic>Chemotherapy</topic><topic>Chromosomes</topic><topic>Cloning</topic><topic>Computational Biology - methods</topic><topic>Disease Models, Animal</topic><topic>Endometrium</topic><topic>Epithelial-Mesenchymal Transition - genetics</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Genotype &amp; 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subjects 13/51
38/39
45/90
631/337/384/331
631/67/1517/1931
64/60
82/80
96/106
96/109
Adenocarcinoma
Angiogenesis
Animal models
Animals
Antitumor agents
Cancer therapies
Carcinosarcoma - genetics
Carcinosarcoma - pathology
Cell Adhesion
Cell Movement
Cell Proliferation
Cell Survival
Chemotherapy
Chromosomes
Cloning
Computational Biology - methods
Disease Models, Animal
Endometrium
Epithelial-Mesenchymal Transition - genetics
Female
Gene expression
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Genotype & phenotype
Humanities and Social Sciences
Humans
Hypotheses
Medical prognosis
Mesenchyme
Mice
MicroRNAs
MicroRNAs - genetics
miRNA
multidisciplinary
Mutation
Neovascularization, Pathologic - genetics
Prognosis
Science
Science (multidisciplinary)
Therapeutic applications
Tumors
Uterine Neoplasms - genetics
Uterine Neoplasms - pathology
Uterus
Xenograft Model Antitumor Assays
Xenografts
title miR-200c-driven Mesenchymal-To-Epithelial Transition is a Therapeutic Target in Uterine Carcinosarcomas
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