Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Medicine / Faculty of Medicine >
Peer-reviewed Journal Articles, etc >
miR-203 inhibits ovarian tumor metastasis by targeting BIRC5 and attenuating the TGFβ pathway
This item is licensed under:Creative Commons Attribution 4.0 International
Title: | miR-203 inhibits ovarian tumor metastasis by targeting BIRC5 and attenuating the TGFβ pathway |
Authors: | Wang, Baojin Browse this author | Li, Xia Browse this author | Zhao, Guannan Browse this author | Yan, Huan Browse this author | Dong, Peixin Browse this author →KAKEN DB | Watari, Hidemichi Browse this author →KAKEN DB | Sims, Michelle Browse this author | Li, Wei Browse this author | Pfeffer, Lawrence M Browse this author | Guo, Yuqi Browse this author | Yue, Junming Browse this author |
Keywords: | miR-203 | Ovarian cancer | Survivin | EMT | Tumor metastasis | Orthotopic ovarian cancer mouse model |
Issue Date: | 21-Sep-2018 |
Publisher: | BioMed Central |
Journal Title: | Journal of Experimental & Clinical Cancer Research |
Volume: | 37 |
Start Page: | 235 |
Publisher DOI: | 10.1186/s13046-018-0906-0 |
Abstract: | Background: We previously reported that miR-203 functions as a tumor suppressor in ovarian cancer cells by directly targeting transcription factor Snai2 and inhibiting epithelial to mesenchymal transition (EMT), whereas BIRC5/survivin promotes EMT. In this study, we tested our hypothesis that miR-203 inhibits ovarian tumor metastasis by suppressing EMT through targeting BIRC5, using an orthotopic ovarian cancer mouse model. Methods: We overexpressed miR-203 in ovarian cancer SKOV3 and OVCAR3 cells using a lentiviral vector and examined cell migration and invasion using transwell plates. The small molecule inhibitor, YM155, was used to inhibit survivin expression. miR-203-expressing and control SKOV3 cells were intrabursally injected into immunocompromised NSG female mice. Primary tumors in ovaries and metastatic tumors were collected to determine the expression of survivin and EMT markers using Western blot and immunostaining. Results: Overexpression of miR-203 inhibits EMT by targeting BIRC5 in ovarian cancer SKOV3 and OVCAR3 cells. miR-203 expression enhances the ability of the survivin inhibitor YM155 to reduce tumor cell migration and invasion in vitro. We further showed that miR-203 expression attenuated the TGFβ pathway in both SKOV3 and OVCAR3 cells. miR-203 expression also inhibited primary tumor growth in ovaries and metastatic tumors in multiple peritoneal organs including liver and spleen. Conclusion: miR-203 inhibits ovarian tumor metastasis by targeting BIRC5/survivin and attenuating the TGFβ pathway. |
Rights: | http://creativecommons.org/licenses/by/4.0/ |
Type: | article |
URI: | http://hdl.handle.net/2115/71519 |
Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
|
Submitter: 董 培新
|