JWA suppresses proliferation in trastuzumab-resistant breast cancer by downregulating CDK12
Abstract Breast cancer is the most common cancer worldwide. JWA is a microtubule-associated protein that has been identified as a tumor suppressor, and its downregulation in tumors is an independent adverse prognostic factor. The objective of this study was to explore the expression, regulation, and...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2021-10-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-021-00693-9 |
| _version_ | 1819030582483484672 |
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| author | Yan Liang Chao Qian Yinghong Xie Xiang Huang Junjie Chen Yanlin Ren Ziyi Fu Yongfei Li Tianyu Zeng Fan Yang Jianwei Zhou Wei Li Yongmei Yin Changqing Wang |
| author_facet | Yan Liang Chao Qian Yinghong Xie Xiang Huang Junjie Chen Yanlin Ren Ziyi Fu Yongfei Li Tianyu Zeng Fan Yang Jianwei Zhou Wei Li Yongmei Yin Changqing Wang |
| author_sort | Yan Liang |
| collection | DOAJ |
| description | Abstract Breast cancer is the most common cancer worldwide. JWA is a microtubule-associated protein that has been identified as a tumor suppressor, and its downregulation in tumors is an independent adverse prognostic factor. The objective of this study was to explore the expression, regulation, and mechanism of JWA in trastuzumab-resistant breast cancers. In this study, we found that JWA expression was lower in trastuzumab-resistant breast cancers than that in trastuzumab-sensitive breast cancers. Furthermore, it was confirmed that overexpression of JWA inhibited proliferation and promoted apoptosis in trastuzumab-resistant breast cancers both in vitro and in vivo. In addition, the low expression of JWA in trastuzumab-resistant breast cancers is associated with a poor prognosis. Combining RNA-sequence datasets and next-generation sequencing, it was found that JWA negatively regulated CDK12, and was involved in the G1-to-S transition of the cell cycle. It has been reported that CDK12 drives breast cancer initiation and induces trastuzumab resistance. Taken together, high expression of JWA could inhibit the growth of trastuzumab-resistant breast cancer, and JWA is a potential predictive marker for trastuzumab resistance. In addition, targeted therapy with JWA may be a novel therapeutic strategy to improve the survival rate of trastuzumab-resistant breast cancer. |
| first_indexed | 2024-12-21T06:32:27Z |
| format | Article |
| id | doaj.art-05ba5004d92c4c27ac9c0b11692a8b42 |
| institution | Directory Open Access Journal |
| issn | 2058-7716 |
| language | English |
| last_indexed | 2024-12-21T06:32:27Z |
| publishDate | 2021-10-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj.art-05ba5004d92c4c27ac9c0b11692a8b422022-12-21T19:12:57ZengNature Publishing GroupCell Death Discovery2058-77162021-10-017111010.1038/s41420-021-00693-9JWA suppresses proliferation in trastuzumab-resistant breast cancer by downregulating CDK12Yan Liang0Chao Qian1Yinghong Xie2Xiang Huang3Junjie Chen4Yanlin Ren5Ziyi Fu6Yongfei Li7Tianyu Zeng8Fan Yang9Jianwei Zhou10Wei Li11Yongmei Yin12Changqing Wang13Department of Oncology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of General Surgery, Sir Run Run HospitalDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical UniversityClinical Medical Research Center, Affiliated Hospital of Nantong UniversityNantong Center for Disease Control and PreventionLaboratory of Breast Disease Department, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of General Surgery, Jiangsu Provincial Hospital of Traditional Chinese MedicineDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Molecular Cell Biology & Toxicology, Center for Global Health, School of Public Health, Nanjing Medical UniversityDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical UniversitySchool of Health Policy and Management, Nanjing Medical UniversityAbstract Breast cancer is the most common cancer worldwide. JWA is a microtubule-associated protein that has been identified as a tumor suppressor, and its downregulation in tumors is an independent adverse prognostic factor. The objective of this study was to explore the expression, regulation, and mechanism of JWA in trastuzumab-resistant breast cancers. In this study, we found that JWA expression was lower in trastuzumab-resistant breast cancers than that in trastuzumab-sensitive breast cancers. Furthermore, it was confirmed that overexpression of JWA inhibited proliferation and promoted apoptosis in trastuzumab-resistant breast cancers both in vitro and in vivo. In addition, the low expression of JWA in trastuzumab-resistant breast cancers is associated with a poor prognosis. Combining RNA-sequence datasets and next-generation sequencing, it was found that JWA negatively regulated CDK12, and was involved in the G1-to-S transition of the cell cycle. It has been reported that CDK12 drives breast cancer initiation and induces trastuzumab resistance. Taken together, high expression of JWA could inhibit the growth of trastuzumab-resistant breast cancer, and JWA is a potential predictive marker for trastuzumab resistance. In addition, targeted therapy with JWA may be a novel therapeutic strategy to improve the survival rate of trastuzumab-resistant breast cancer.https://doi.org/10.1038/s41420-021-00693-9 |
| spellingShingle | Yan Liang Chao Qian Yinghong Xie Xiang Huang Junjie Chen Yanlin Ren Ziyi Fu Yongfei Li Tianyu Zeng Fan Yang Jianwei Zhou Wei Li Yongmei Yin Changqing Wang JWA suppresses proliferation in trastuzumab-resistant breast cancer by downregulating CDK12 Cell Death Discovery |
| title | JWA suppresses proliferation in trastuzumab-resistant breast cancer by downregulating CDK12 |
| title_full | JWA suppresses proliferation in trastuzumab-resistant breast cancer by downregulating CDK12 |
| title_fullStr | JWA suppresses proliferation in trastuzumab-resistant breast cancer by downregulating CDK12 |
| title_full_unstemmed | JWA suppresses proliferation in trastuzumab-resistant breast cancer by downregulating CDK12 |
| title_short | JWA suppresses proliferation in trastuzumab-resistant breast cancer by downregulating CDK12 |
| title_sort | jwa suppresses proliferation in trastuzumab resistant breast cancer by downregulating cdk12 |
| url | https://doi.org/10.1038/s41420-021-00693-9 |
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