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miR-203 inhibits ovarian tumor metastasis by targeting BIRC5 and attenuating the TGFβ pathway

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Please use this identifier to cite or link to this item:http://hdl.handle.net/2115/71519

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

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