Targeting the circBMPR2/miR-553/USP4 Axis as a Potent Therapeutic Approach for Breast Cancer
Emerging evidence suggests that circular RNAs (circRNAs) have crucial roles in various processes, including cancer development and progression. However, the functional roles of circRNAs in breast cancer remain to be elucidated. In this study, we identified a novel circRNA (named circBMPR2) whose exp...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-09-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253119301350 |
| _version_ | 1818511624585084928 |
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| author | Yiran Liang Xiaojin Song Yaming Li Tingting Ma Peng Su Renbo Guo Bing Chen Hanwen Zhang Yuting Sang Ying Liu Yi Duan Ning Zhang Xiaoyan Li Wenjing Zhao Lijuan Wang Qifeng Yang |
| author_facet | Yiran Liang Xiaojin Song Yaming Li Tingting Ma Peng Su Renbo Guo Bing Chen Hanwen Zhang Yuting Sang Ying Liu Yi Duan Ning Zhang Xiaoyan Li Wenjing Zhao Lijuan Wang Qifeng Yang |
| author_sort | Yiran Liang |
| collection | DOAJ |
| description | Emerging evidence suggests that circular RNAs (circRNAs) have crucial roles in various processes, including cancer development and progression. However, the functional roles of circRNAs in breast cancer remain to be elucidated. In this study, we identified a novel circRNA (named circBMPR2) whose expression was lower in breast cancer tissues with metastasis. Moreover, circBMPR2 expression was negatively associated with the motility of breast cancer cells and significantly downregulated in human breast cancer tissues. Functionally, we found that circBMPR2 knockdown effectively enhanced cell proliferation, migration, and invasion. Moreover, circBMPR2 knockdown promoted tamoxifen resistance of breast cancer cells through inhibiting tamoxifen-induced apoptosis, whereas circBMPR2 overexpression led to decreased tamoxifen resistance. Mechanistically, we demonstrated that circBMPR2 could abundantly sponge miR-553 and that miR-553 overexpression could attenuate the inhibitory effects caused by circBMPR2 overexpression. We also found that ubiquitin-specific protease 4 (USP4) was a direct target of miR-553, which functions as a tumor suppressor in breast cancer. Our findings demonstrated that circBMPR2 might function as a miR-553 sponge and then relieve the suppression of USP4 to inhibit the progression and tamoxifen resistance of breast cancer. Targeting this newly identified circRNA may help us to develop potential novel therapies for breast cancer patients. Keywords: breast cancer, circBMPR2, tumor suppressor, tamoxifen resistance, miR-553, USP4 |
| first_indexed | 2024-12-10T23:35:37Z |
| format | Article |
| id | doaj.art-81f61d2fca83490587801c768a855e9d |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-12-10T23:35:37Z |
| publishDate | 2019-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-81f61d2fca83490587801c768a855e9d2022-12-22T01:29:12ZengElsevierMolecular Therapy: Nucleic Acids2162-25312019-09-0117347361Targeting the circBMPR2/miR-553/USP4 Axis as a Potent Therapeutic Approach for Breast CancerYiran Liang0Xiaojin Song1Yaming Li2Tingting Ma3Peng Su4Renbo Guo5Bing Chen6Hanwen Zhang7Yuting Sang8Ying Liu9Yi Duan10Ning Zhang11Xiaoyan Li12Wenjing Zhao13Lijuan Wang14Qifeng Yang15Department of Breast Surgery, Qilu Hospital, Shandong University, Shandong, ChinaDepartment of Breast Surgery, Qilu Hospital, Shandong University, Shandong, ChinaDepartment of Breast Surgery, Qilu Hospital, Shandong University, Shandong, ChinaDepartment of Breast Surgery, Qilu Hospital, Shandong University, Shandong, ChinaDepartment of Pathology, Qilu Hospital, Shandong University, Shandong, ChinaDepartment of Urology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong, ChinaPathology Tissue Bank, Qilu Hospital, Shandong University, Shandong, ChinaDepartment of Breast Surgery, Qilu Hospital, Shandong University, Shandong, ChinaDepartment of Breast Surgery, Qilu Hospital, Shandong University, Shandong, ChinaDepartment of Breast Surgery, Qilu Hospital, Shandong University, Shandong, ChinaDepartment of Breast Surgery, Qilu Hospital, Shandong University, Shandong, ChinaDepartment of Breast Surgery, Qilu Hospital, Shandong University, Shandong, ChinaDepartment of Breast Surgery, Qilu Hospital, Shandong University, Shandong, ChinaPathology Tissue Bank, Qilu Hospital, Shandong University, Shandong, ChinaPathology Tissue Bank, Qilu Hospital, Shandong University, Shandong, ChinaDepartment of Breast Surgery, Qilu Hospital, Shandong University, Shandong, China; Pathology Tissue Bank, Qilu Hospital, Shandong University, Shandong, China; Corresponding author: Qifeng Yang, Department of Breast Surgery, Qilu Hospital, Shandong University, Wenhua Xi Road 107, Jinan 250012, Shandong, China.Emerging evidence suggests that circular RNAs (circRNAs) have crucial roles in various processes, including cancer development and progression. However, the functional roles of circRNAs in breast cancer remain to be elucidated. In this study, we identified a novel circRNA (named circBMPR2) whose expression was lower in breast cancer tissues with metastasis. Moreover, circBMPR2 expression was negatively associated with the motility of breast cancer cells and significantly downregulated in human breast cancer tissues. Functionally, we found that circBMPR2 knockdown effectively enhanced cell proliferation, migration, and invasion. Moreover, circBMPR2 knockdown promoted tamoxifen resistance of breast cancer cells through inhibiting tamoxifen-induced apoptosis, whereas circBMPR2 overexpression led to decreased tamoxifen resistance. Mechanistically, we demonstrated that circBMPR2 could abundantly sponge miR-553 and that miR-553 overexpression could attenuate the inhibitory effects caused by circBMPR2 overexpression. We also found that ubiquitin-specific protease 4 (USP4) was a direct target of miR-553, which functions as a tumor suppressor in breast cancer. Our findings demonstrated that circBMPR2 might function as a miR-553 sponge and then relieve the suppression of USP4 to inhibit the progression and tamoxifen resistance of breast cancer. Targeting this newly identified circRNA may help us to develop potential novel therapies for breast cancer patients. Keywords: breast cancer, circBMPR2, tumor suppressor, tamoxifen resistance, miR-553, USP4http://www.sciencedirect.com/science/article/pii/S2162253119301350 |
| spellingShingle | Yiran Liang Xiaojin Song Yaming Li Tingting Ma Peng Su Renbo Guo Bing Chen Hanwen Zhang Yuting Sang Ying Liu Yi Duan Ning Zhang Xiaoyan Li Wenjing Zhao Lijuan Wang Qifeng Yang Targeting the circBMPR2/miR-553/USP4 Axis as a Potent Therapeutic Approach for Breast Cancer Molecular Therapy: Nucleic Acids |
| title | Targeting the circBMPR2/miR-553/USP4 Axis as a Potent Therapeutic Approach for Breast Cancer |
| title_full | Targeting the circBMPR2/miR-553/USP4 Axis as a Potent Therapeutic Approach for Breast Cancer |
| title_fullStr | Targeting the circBMPR2/miR-553/USP4 Axis as a Potent Therapeutic Approach for Breast Cancer |
| title_full_unstemmed | Targeting the circBMPR2/miR-553/USP4 Axis as a Potent Therapeutic Approach for Breast Cancer |
| title_short | Targeting the circBMPR2/miR-553/USP4 Axis as a Potent Therapeutic Approach for Breast Cancer |
| title_sort | targeting the circbmpr2 mir 553 usp4 axis as a potent therapeutic approach for breast cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2162253119301350 |
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