miR-454 suppresses the proliferation and invasion of ovarian cancer by targeting E2F6
Abstract Background The aberrant expression of microRNA-454 (miR-454) has been confirmed to be involved in the development of cancers. However, the functional role of miR-454 in the progression of ovarian cancer remains unclear. Methods The expression of miR-454 in ovarian cancer cells and serum of...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-06-01
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| Series: | Cancer Cell International |
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| Online Access: | http://link.springer.com/article/10.1186/s12935-020-01300-0 |
| _version_ | 1818162002635259904 |
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| author | Yunhe An Jun Zhang Xiaoyan Cheng Baoming Li Yanjie Tian Xiaoli Zhang Fangqi Zhao |
| author_facet | Yunhe An Jun Zhang Xiaoyan Cheng Baoming Li Yanjie Tian Xiaoli Zhang Fangqi Zhao |
| author_sort | Yunhe An |
| collection | DOAJ |
| description | Abstract Background The aberrant expression of microRNA-454 (miR-454) has been confirmed to be involved in the development of cancers. However, the functional role of miR-454 in the progression of ovarian cancer remains unclear. Methods The expression of miR-454 in ovarian cancer cells and serum of ovarian cancer patients was detected by RT-PCR. CCK8, colony formation, transwell, and flow cytometry assays were conducted to assess the effects of miR-454 on ovarian cancer cell proliferation, migration, invasion, and apoptosis, respectively. Dual-luciferase reporter assay was used to confirm the targeting relationship between miR-454 and E2F6. The expression pattern of E2F6 in ovarian cancer tissues was detected using immunohistochemistry (IHC) assay. The relative expression of related proteins was examined using western blot analysis. Results miR-454 was markedly down-regulated by hypoxia in ovarian cancer cells. Compared with normal samples, the expression of miR-454 was up-regulated in the serum of ovarian cancer patients, and correlated with the clinicopathological stages of ovarian cancer. Next, we found that miR-454 overexpression inhibited the proliferation, migration and invasion of OVCAR3 and SKOV3 cells, as well as promoted apoptosis. In addition, the Akt/mTOR and Wnt/β-catenin signaling pathway were inhibited by miR-454 in ovarian cancer cells. Mechanically, bioinformatic analysis and dual-luciferase reporter assay confirmed that E2F6 was a direct target of miR-454 and negatively regulated by miR-454 in ovarian cancer cells. Moreover, IHC analysis showed that E2F6 was highly expressed in ovarian cancer tissues. Finally, we found that the increasing cell proliferation and migration triggered by E2F6 overexpression were abolished by miR-454 overexpression. Conclusion Taken together, these results highlight the role of miR-454 as a tumor suppressor in ovarian cancer cells by targeting E2F6, indicating that miR-454 may be a potential diagnostic biomarker and therapeutic target for ovarian cancer. |
| first_indexed | 2024-12-11T16:26:44Z |
| format | Article |
| id | doaj.art-772c01704b8f46fba5c31661321a486d |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-12-11T16:26:44Z |
| publishDate | 2020-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-772c01704b8f46fba5c31661321a486d2022-12-22T00:58:41ZengBMCCancer Cell International1475-28672020-06-0120111010.1186/s12935-020-01300-0miR-454 suppresses the proliferation and invasion of ovarian cancer by targeting E2F6Yunhe An0Jun Zhang1Xiaoyan Cheng2Baoming Li3Yanjie Tian4Xiaoli Zhang5Fangqi Zhao6Department of Biotechnology, Beijing Center for Physical and Chemical AnalysisDepartment of Obstetrics and Gynecology, Beijing Anzhen Hospital, Capital Medical UniversityDepartment of Biotechnology, Beijing Center for Physical and Chemical AnalysisDepartment of Biotechnology, Beijing Center for Physical and Chemical AnalysisDepartment of Biotechnology, Beijing Center for Physical and Chemical AnalysisDepartment of Biotechnology, Beijing Center for Physical and Chemical AnalysisDepartment of Obstetrics and Gynecology, Beijing Anzhen Hospital, Capital Medical UniversityAbstract Background The aberrant expression of microRNA-454 (miR-454) has been confirmed to be involved in the development of cancers. However, the functional role of miR-454 in the progression of ovarian cancer remains unclear. Methods The expression of miR-454 in ovarian cancer cells and serum of ovarian cancer patients was detected by RT-PCR. CCK8, colony formation, transwell, and flow cytometry assays were conducted to assess the effects of miR-454 on ovarian cancer cell proliferation, migration, invasion, and apoptosis, respectively. Dual-luciferase reporter assay was used to confirm the targeting relationship between miR-454 and E2F6. The expression pattern of E2F6 in ovarian cancer tissues was detected using immunohistochemistry (IHC) assay. The relative expression of related proteins was examined using western blot analysis. Results miR-454 was markedly down-regulated by hypoxia in ovarian cancer cells. Compared with normal samples, the expression of miR-454 was up-regulated in the serum of ovarian cancer patients, and correlated with the clinicopathological stages of ovarian cancer. Next, we found that miR-454 overexpression inhibited the proliferation, migration and invasion of OVCAR3 and SKOV3 cells, as well as promoted apoptosis. In addition, the Akt/mTOR and Wnt/β-catenin signaling pathway were inhibited by miR-454 in ovarian cancer cells. Mechanically, bioinformatic analysis and dual-luciferase reporter assay confirmed that E2F6 was a direct target of miR-454 and negatively regulated by miR-454 in ovarian cancer cells. Moreover, IHC analysis showed that E2F6 was highly expressed in ovarian cancer tissues. Finally, we found that the increasing cell proliferation and migration triggered by E2F6 overexpression were abolished by miR-454 overexpression. Conclusion Taken together, these results highlight the role of miR-454 as a tumor suppressor in ovarian cancer cells by targeting E2F6, indicating that miR-454 may be a potential diagnostic biomarker and therapeutic target for ovarian cancer.http://link.springer.com/article/10.1186/s12935-020-01300-0Ovarian cancermiR-454E2F6GrowthMetastasis |
| spellingShingle | Yunhe An Jun Zhang Xiaoyan Cheng Baoming Li Yanjie Tian Xiaoli Zhang Fangqi Zhao miR-454 suppresses the proliferation and invasion of ovarian cancer by targeting E2F6 Cancer Cell International Ovarian cancer miR-454 E2F6 Growth Metastasis |
| title | miR-454 suppresses the proliferation and invasion of ovarian cancer by targeting E2F6 |
| title_full | miR-454 suppresses the proliferation and invasion of ovarian cancer by targeting E2F6 |
| title_fullStr | miR-454 suppresses the proliferation and invasion of ovarian cancer by targeting E2F6 |
| title_full_unstemmed | miR-454 suppresses the proliferation and invasion of ovarian cancer by targeting E2F6 |
| title_short | miR-454 suppresses the proliferation and invasion of ovarian cancer by targeting E2F6 |
| title_sort | mir 454 suppresses the proliferation and invasion of ovarian cancer by targeting e2f6 |
| topic | Ovarian cancer miR-454 E2F6 Growth Metastasis |
| url | http://link.springer.com/article/10.1186/s12935-020-01300-0 |
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