| RRC ID |
65935
|
| 著者 |
Tseng JH, Bisogna M, Hoang LN, Olvera N, Rodriguez-Aguayo C, Lopez-Berestein G, Sood AK, Levine DA, Jelinic P.
|
| タイトル |
miR-200c-driven Mesenchymal-To-Epithelial Transition is a Therapeutic Target in Uterine Carcinosarcomas.
|
| ジャーナル |
Sci Rep
|
| 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.
|
| 巻・号 |
7(1)
|
| ページ |
3614
|
| 公開日 |
2017-6-15
|
| DOI |
10.1038/s41598-017-03972-7
|
| PII |
10.1038/s41598-017-03972-7
|
| PMID |
28620240
|
| PMC |
PMC5472620
|
| MeSH |
Animals
Carcinosarcoma / genetics*
Carcinosarcoma / pathology*
Cell Adhesion
Cell Movement
Cell Proliferation
Cell Survival
Computational Biology / methods
Disease Models, Animal
Epithelial-Mesenchymal Transition / genetics*
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Mice
MicroRNAs / genetics*
Mutation
Neovascularization, Pathologic / genetics
Uterine Neoplasms / genetics*
Uterine Neoplasms / pathology*
Xenograft Model Antitumor Assays
|
| IF |
3.998
|
| リソース情報 |
| ヒト・動物細胞 |
JHUCS-1(RCB1547) |
