Metapristone (RU486-derivative) inhibits endometrial cancer cell progress through regulating miR-492/Klf5/Nrf1 axis
Abstract Background Endometrial cancer is an invasive gynecological cancer prevalent in the world. The pathogenesis of endometrial cancer is related to multiple levels of regulation, referring to oestrogen, tumor-suppressor gene (e.g. PTEN) or microRNAs (e.g. miR-23a and miR-29b). Metapristone is a...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-01-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-020-01682-1 |
| _version_ | 1818453007427174400 |
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| author | Yue Chang Min Hao Ru Jia Yihui Zhao Yixuan Cai Yun Liu |
| author_facet | Yue Chang Min Hao Ru Jia Yihui Zhao Yixuan Cai Yun Liu |
| author_sort | Yue Chang |
| collection | DOAJ |
| description | Abstract Background Endometrial cancer is an invasive gynecological cancer prevalent in the world. The pathogenesis of endometrial cancer is related to multiple levels of regulation, referring to oestrogen, tumor-suppressor gene (e.g. PTEN) or microRNAs (e.g. miR-23a and miR-29b). Metapristone is a hormone-related drug, which is widely used in clinical treatment of endometrial cancer. However, the underlying regulatory mechanism of metapristone on endometrial cancer is still unclear, especially the regulatory effect on microRNAs. The aim of this study is to investigate the specific molecular mechanism of metapristone regulating microRNAs in the treatment of endometrial cancer. Methods RL95-2 cells and Ishikawa cells were used as the endometrial cancer models. MiR-492 or si-miR-492 was transfected into RL95-2 cells and Ishikawa cells to explore the role of miR-492 in endometrial cancer. The cell cancer model and mice cancer model were used to confirm the function and mechanism of metapristone affected on endometrial cancer in vitro and in vivo. Mechanically, cell proliferation was monitored using MTT assay, cell colony formation assay and EdU assay. Luciferase reporter assay was used to identify the downstream target gene of miR-492. The protein expression and RNA expression were respectively measured by western blot and qRT-PCR for cell signaling pathway research, subsequently, were verified in the mice tumor model via immunohistochemistry. Results Metapristone as a kind of hormone-related drug significantly inhibited the endometrial cancer cell growth through regulating cell apoptosis-related gene expression. Mechanically, miR-492 and its target genes Klf5 and Nrf1 were highly expressed in the endometrial cancer cell lines, which promoted cell proliferation and inhibited cell apoptosis. Metapristone decreased the expression of miR-492 and its target genes Klf5 and Nrf1, leading to endometrial cancer cell growth inhibition in vitro and in vivo. Conclusion Metapristone inhibited the endometrial cancer cell growth through regulating the cell apoptosis-related signaling pathway and decreasing the expression of miR-492 and its downstream target genes (Klf5 and Nrf1), which provided the theoretical basis in clinical treatment of endometrial cancer. |
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| id | doaj.art-5f32dc1f3da342cdbab107688c6d9aa8 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-12-14T21:32:08Z |
| publishDate | 2021-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-5f32dc1f3da342cdbab107688c6d9aa82022-12-21T22:46:40ZengBMCCancer Cell International1475-28672021-01-0121111410.1186/s12935-020-01682-1Metapristone (RU486-derivative) inhibits endometrial cancer cell progress through regulating miR-492/Klf5/Nrf1 axisYue Chang0Min Hao1Ru Jia2Yihui Zhao3Yixuan Cai4Yun Liu5Department of Obstetrics and Gynecology, Beijing Friendship Hospital Affiliated to Capital Medical UniversityDepartment of Obstetrics and Gynecology, Beijing Friendship Hospital Affiliated to Capital Medical UniversityDepartment of Obstetrics and Gynecology, Beijing Friendship Hospital Affiliated to Capital Medical UniversityDepartment of Obstetrics and Gynecology, Beijing Friendship Hospital Affiliated to Capital Medical UniversityDepartment of Obstetrics and Gynecology, Beijing Friendship Hospital Affiliated to Capital Medical UniversityDepartment of Obstetrics and Gynecology, Beijing Friendship Hospital Affiliated to Capital Medical UniversityAbstract Background Endometrial cancer is an invasive gynecological cancer prevalent in the world. The pathogenesis of endometrial cancer is related to multiple levels of regulation, referring to oestrogen, tumor-suppressor gene (e.g. PTEN) or microRNAs (e.g. miR-23a and miR-29b). Metapristone is a hormone-related drug, which is widely used in clinical treatment of endometrial cancer. However, the underlying regulatory mechanism of metapristone on endometrial cancer is still unclear, especially the regulatory effect on microRNAs. The aim of this study is to investigate the specific molecular mechanism of metapristone regulating microRNAs in the treatment of endometrial cancer. Methods RL95-2 cells and Ishikawa cells were used as the endometrial cancer models. MiR-492 or si-miR-492 was transfected into RL95-2 cells and Ishikawa cells to explore the role of miR-492 in endometrial cancer. The cell cancer model and mice cancer model were used to confirm the function and mechanism of metapristone affected on endometrial cancer in vitro and in vivo. Mechanically, cell proliferation was monitored using MTT assay, cell colony formation assay and EdU assay. Luciferase reporter assay was used to identify the downstream target gene of miR-492. The protein expression and RNA expression were respectively measured by western blot and qRT-PCR for cell signaling pathway research, subsequently, were verified in the mice tumor model via immunohistochemistry. Results Metapristone as a kind of hormone-related drug significantly inhibited the endometrial cancer cell growth through regulating cell apoptosis-related gene expression. Mechanically, miR-492 and its target genes Klf5 and Nrf1 were highly expressed in the endometrial cancer cell lines, which promoted cell proliferation and inhibited cell apoptosis. Metapristone decreased the expression of miR-492 and its target genes Klf5 and Nrf1, leading to endometrial cancer cell growth inhibition in vitro and in vivo. Conclusion Metapristone inhibited the endometrial cancer cell growth through regulating the cell apoptosis-related signaling pathway and decreasing the expression of miR-492 and its downstream target genes (Klf5 and Nrf1), which provided the theoretical basis in clinical treatment of endometrial cancer.https://doi.org/10.1186/s12935-020-01682-1Endometrial cancermiR-492MetapristoneKlf5Nrf1 |
| spellingShingle | Yue Chang Min Hao Ru Jia Yihui Zhao Yixuan Cai Yun Liu Metapristone (RU486-derivative) inhibits endometrial cancer cell progress through regulating miR-492/Klf5/Nrf1 axis Cancer Cell International Endometrial cancer miR-492 Metapristone Klf5 Nrf1 |
| title | Metapristone (RU486-derivative) inhibits endometrial cancer cell progress through regulating miR-492/Klf5/Nrf1 axis |
| title_full | Metapristone (RU486-derivative) inhibits endometrial cancer cell progress through regulating miR-492/Klf5/Nrf1 axis |
| title_fullStr | Metapristone (RU486-derivative) inhibits endometrial cancer cell progress through regulating miR-492/Klf5/Nrf1 axis |
| title_full_unstemmed | Metapristone (RU486-derivative) inhibits endometrial cancer cell progress through regulating miR-492/Klf5/Nrf1 axis |
| title_short | Metapristone (RU486-derivative) inhibits endometrial cancer cell progress through regulating miR-492/Klf5/Nrf1 axis |
| title_sort | metapristone ru486 derivative inhibits endometrial cancer cell progress through regulating mir 492 klf5 nrf1 axis |
| topic | Endometrial cancer miR-492 Metapristone Klf5 Nrf1 |
| url | https://doi.org/10.1186/s12935-020-01682-1 |
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