miR-200c-driven mesenchymal-to-epithelial transition is a therapeutic target in uterine carcinosarcomas Journal Article
| Authors: | Tseng, J. H.; Bisogna, M.; Hoang, L. N.; Olvera, N.; Rodriguez-Aguayo, C.; Lopez-Berestein, G.; Sood, A. K.; Levine, D. A.; Jelinic, P. |
| Article Title: | 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 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. © 2017 The Author(s). |
| Journal Title: | Scientific Reports |
| Volume: | 7 |
| ISSN: | 2045-2322 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2017-06-15 |
| Start Page: | 3614 |
| Language: | English |
| DOI: | 10.1038/s41598-017-03972-7 |
| PROVIDER: | scopus |
| PMCID: | PMC5472620 |
| PUBMED: | 28620240 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 August 2017 -- Source: Scopus |
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