The deubiquitinase BRCC3 increases the stability of ZEB1 and promotes the proliferation and metastasis of triple-negative breast cancer cells
Triple negative breast cancer (TNBC) has a high recurrence rate, metastasis rate and mortality rate. The aim of this study is to identify new targets for the treatment of TNBC. Clinical samples are used for screening deubiquitinating enzymes (DUBs). MDA-MB-231 cells and a TNBC mouse model are used f...
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| Format: | Article |
| Language: | English |
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China Science Publishing & Media Ltd.
2024-03-01
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| Series: | Acta Biochimica et Biophysica Sinica |
| Subjects: | |
| Online Access: | https://www.sciengine.com/doi/10.3724/abbs.2024005 |
| _version_ | 1797208493318471680 |
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| author | Huang Qidi Zheng Shurong Gu Huayan Yang Zhi Lu Yiqiao Yu Xia Guo Guilong |
| author_facet | Huang Qidi Zheng Shurong Gu Huayan Yang Zhi Lu Yiqiao Yu Xia Guo Guilong |
| author_sort | Huang Qidi |
| collection | DOAJ |
| description | Triple negative breast cancer (TNBC) has a high recurrence rate, metastasis rate and mortality rate. The aim of this study is to identify new targets for the treatment of TNBC. Clinical samples are used for screening deubiquitinating enzymes (DUBs). MDA-MB-231 cells and a TNBC mouse model are used for in vitro and in vivo experiments, respectively. Western blot analysis is used to detect the protein expressions of DUBs, zinc finger E-box binding homeobox 1 (ZEB1), and epithelial-mesenchymal transition (EMT)-related markers. Colony formation and transwell assays are used to detect the proliferation, migration and invasion of TNBC cells. Wound healing assay is used to detect the mobility of TNBC cells. Immunoprecipitation assay is used to detect the interaction between breast cancer susceptibility gene 1/2-containing complex subunit 3 (BRCC3) and ZEB1. ZEB1 ubiquitination levels, protein stability, and protein degradation are also examined. Pathological changes in the lung tissues are detected via HE staining. Our results show a significant positive correlation between the expressions of BRCC3 and ZEB1 in clinical TNBC tissues. Interference with BRCC3 inhibits TNBC cell proliferation, migration, invasion and EMT. BRCC3 interacts with ZEB1 and interferes with BRCC3 to inhibit ZEB1 expression by increasing ZEB1 ubiquitination. Interference with BRCC3 inhibits TNBC cell tumorigenesis and lung metastasis in vivo. In all, this study demonstrates that BRCC3 can increase the stability of ZEB1, upregulate ZEB1 expression, and promote the proliferation, migration, invasion, EMT, and metastasis of TNBC cells, providing a new direction for cancer therapy. |
| first_indexed | 2024-04-24T09:39:41Z |
| format | Article |
| id | doaj.art-46c316c9f589455b9d194618ccfb2219 |
| institution | Directory Open Access Journal |
| issn | 1672-9145 |
| language | English |
| last_indexed | 2024-04-24T09:39:41Z |
| publishDate | 2024-03-01 |
| publisher | China Science Publishing & Media Ltd. |
| record_format | Article |
| series | Acta Biochimica et Biophysica Sinica |
| spelling | doaj.art-46c316c9f589455b9d194618ccfb22192024-04-15T07:14:54ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452024-03-015656457510.3724/abbs.202400520d259ccThe deubiquitinase BRCC3 increases the stability of ZEB1 and promotes the proliferation and metastasis of triple-negative breast cancer cellsHuang Qidi0Zheng Shurong1Gu Huayan2Yang Zhi3Lu Yiqiao4Yu Xia5Guo Guilong6["Department of Breast Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China"]["Department of Breast Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China"]["Department of Breast Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China"]["Department of Breast Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China"]["Department of Breast Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China"]["Department of Pathology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China"]["Department of Breast Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China"]Triple negative breast cancer (TNBC) has a high recurrence rate, metastasis rate and mortality rate. The aim of this study is to identify new targets for the treatment of TNBC. Clinical samples are used for screening deubiquitinating enzymes (DUBs). MDA-MB-231 cells and a TNBC mouse model are used for in vitro and in vivo experiments, respectively. Western blot analysis is used to detect the protein expressions of DUBs, zinc finger E-box binding homeobox 1 (ZEB1), and epithelial-mesenchymal transition (EMT)-related markers. Colony formation and transwell assays are used to detect the proliferation, migration and invasion of TNBC cells. Wound healing assay is used to detect the mobility of TNBC cells. Immunoprecipitation assay is used to detect the interaction between breast cancer susceptibility gene 1/2-containing complex subunit 3 (BRCC3) and ZEB1. ZEB1 ubiquitination levels, protein stability, and protein degradation are also examined. Pathological changes in the lung tissues are detected via HE staining. Our results show a significant positive correlation between the expressions of BRCC3 and ZEB1 in clinical TNBC tissues. Interference with BRCC3 inhibits TNBC cell proliferation, migration, invasion and EMT. BRCC3 interacts with ZEB1 and interferes with BRCC3 to inhibit ZEB1 expression by increasing ZEB1 ubiquitination. Interference with BRCC3 inhibits TNBC cell tumorigenesis and lung metastasis in vivo. In all, this study demonstrates that BRCC3 can increase the stability of ZEB1, upregulate ZEB1 expression, and promote the proliferation, migration, invasion, EMT, and metastasis of TNBC cells, providing a new direction for cancer therapy.https://www.sciengine.com/doi/10.3724/abbs.2024005BRCC3ZEB1epithelial-mesenchymal transitiontriple negative breast cancer |
| spellingShingle | Huang Qidi Zheng Shurong Gu Huayan Yang Zhi Lu Yiqiao Yu Xia Guo Guilong The deubiquitinase BRCC3 increases the stability of ZEB1 and promotes the proliferation and metastasis of triple-negative breast cancer cells Acta Biochimica et Biophysica Sinica BRCC3 ZEB1 epithelial-mesenchymal transition triple negative breast cancer |
| title | The deubiquitinase BRCC3 increases the stability of ZEB1 and promotes the proliferation and metastasis of triple-negative breast cancer cells |
| title_full | The deubiquitinase BRCC3 increases the stability of ZEB1 and promotes the proliferation and metastasis of triple-negative breast cancer cells |
| title_fullStr | The deubiquitinase BRCC3 increases the stability of ZEB1 and promotes the proliferation and metastasis of triple-negative breast cancer cells |
| title_full_unstemmed | The deubiquitinase BRCC3 increases the stability of ZEB1 and promotes the proliferation and metastasis of triple-negative breast cancer cells |
| title_short | The deubiquitinase BRCC3 increases the stability of ZEB1 and promotes the proliferation and metastasis of triple-negative breast cancer cells |
| title_sort | deubiquitinase brcc3 increases the stability of zeb1 and promotes the proliferation and metastasis of triple negative breast cancer cells |
| topic | BRCC3 ZEB1 epithelial-mesenchymal transition triple negative breast cancer |
| url | https://www.sciengine.com/doi/10.3724/abbs.2024005 |
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