BRD7 suppresses invasion and metastasis in breast cancer by negatively regulating YB1-induced epithelial-mesenchymal transition
Abstract Background BRD7 is a tumor suppressor known to inhibit cell proliferation and cell cycle progression and initiate apoptosis in breast cancer. However, the function and underlying molecular events of BRD7 in tumor invasion and metastasis in breast cancer are not fully understood. Methods BRD...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-02-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13046-019-1493-4 |
| _version_ | 1818920345239814144 |
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| author | Weihong Niu Yanwei Luo Yao Zhou Mengna Li Chunchun Wu Yumei Duan Heran Wang Songqing Fan Zheng Li Wei Xiong Xiaoling Li Guiyuan Li Caiping Ren Hui Li Ming Zhou |
| author_facet | Weihong Niu Yanwei Luo Yao Zhou Mengna Li Chunchun Wu Yumei Duan Heran Wang Songqing Fan Zheng Li Wei Xiong Xiaoling Li Guiyuan Li Caiping Ren Hui Li Ming Zhou |
| author_sort | Weihong Niu |
| collection | DOAJ |
| description | Abstract Background BRD7 is a tumor suppressor known to inhibit cell proliferation and cell cycle progression and initiate apoptosis in breast cancer. However, the function and underlying molecular events of BRD7 in tumor invasion and metastasis in breast cancer are not fully understood. Methods BRD7 expression was assessed in two stable cell lines MDA231 and MCF7 with BRD7 overexpression and one stable cell line MDA231 with BRD7 interference using qRT-PCR and western blotting. CCK8 assay was used to examine the proliferation ability of MDA231 and MCF7 cells. Scratch wound healing assay was used to evaluate cell migration in MDA231 and MCF7 cells. Both Matrigel and three-dimensional invasion assays were performed to investigate the cell invasion ability after BRD7 overexpression or silencing or YB1 restoration in MDA231 and MCF7 cells. The potential interacting proteins of BRD7 were screened using co-immunoprecipitation combined with mass spectrometry and verified by co-immunoprecipitation in HEK293T cells. Additionally, we confirmed the specific binding region between BRD7 and YB1 in HEK293T cells by constructing a series of deletion mutants of BRD7 and YB1 respectively. Finally, xenograft and metastatic mouse models using MDA231 cells were established to confirm the effect of BRD7 on tumor growth and metastasis. Results Here, the results of a series of assays in vitro indicated that BRD7 has the ability to inhibit the mobility, migration and invasion of breast cancer cells. In addition, YB1 was identified as a novel interacting protein of BRD7, and BRD7 was found to associate with the C-terminus of YB1 via its N-terminus. BRD7 decreases the expression of YB1 through negatively regulating YB1 phosphorylation at Ser102, thereby promoting its proteasomal degradation. Furthermore, gene set enrichment analysis revealed that epithelial-mesenchymal transition (EMT) is the common change occurring with altered expression of either BRD7 or YB1 and that BRD7 represses mesenchymal genes and activates epithelial genes. Moreover, restoring the expression of YB1 antagonized the inhibitory effect of BRD7 on tumorigenicity, EMT, invasiveness and metastasis through a series of in vitro and in vivo experiments. Additionally, BRD7 expression was negatively correlated with the level of YB1 in breast cancer patients. The combination of low BRD7 and high YB1 expression was significantly associated with poor prognosis, distant metastasis and advanced TNM stage. Conclusions Collectively, these findings uncover that BRD7 blocks tumor growth, migration and metastasis by negatively regulating YB1-induced EMT, providing new insights into the mechanism by which BRD7 contributes to the progression and metastasis of breast cancer. |
| first_indexed | 2024-12-20T01:20:16Z |
| format | Article |
| id | doaj.art-deff3a0f8cf242afaa4bc367b8f1c006 |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-12-20T01:20:16Z |
| publishDate | 2020-02-01 |
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| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-deff3a0f8cf242afaa4bc367b8f1c0062022-12-21T19:58:27ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662020-02-0139111910.1186/s13046-019-1493-4BRD7 suppresses invasion and metastasis in breast cancer by negatively regulating YB1-induced epithelial-mesenchymal transitionWeihong Niu0Yanwei Luo1Yao Zhou2Mengna Li3Chunchun Wu4Yumei Duan5Heran Wang6Songqing Fan7Zheng Li8Wei Xiong9Xiaoling Li10Guiyuan Li11Caiping Ren12Hui Li13Ming Zhou14The Affiliated Tumor Hospital of Xiangya Medical School, Central South UniversityCancer Research Institute, School of Basic Medical Sciences, Central South UniversityThe Affiliated Tumor Hospital of Xiangya Medical School, Central South UniversityCancer Research Institute, School of Basic Medical Sciences, Central South UniversityCancer Research Institute, School of Basic Medical Sciences, Central South UniversityCancer Research Institute, School of Basic Medical Sciences, Central South UniversityThe Affiliated Tumor Hospital of Xiangya Medical School, Central South UniversityThe Second Xiang-Ya Hospital, Central South UniversityCancer Research Institute, School of Basic Medical Sciences, Central South UniversityCancer Research Institute, School of Basic Medical Sciences, Central South UniversityCancer Research Institute, School of Basic Medical Sciences, Central South UniversityThe Affiliated Tumor Hospital of Xiangya Medical School, Central South UniversityCancer Research Institute, School of Basic Medical Sciences, Central South UniversityThe Second Xiang-Ya Hospital, Central South UniversityThe Affiliated Tumor Hospital of Xiangya Medical School, Central South UniversityAbstract Background BRD7 is a tumor suppressor known to inhibit cell proliferation and cell cycle progression and initiate apoptosis in breast cancer. However, the function and underlying molecular events of BRD7 in tumor invasion and metastasis in breast cancer are not fully understood. Methods BRD7 expression was assessed in two stable cell lines MDA231 and MCF7 with BRD7 overexpression and one stable cell line MDA231 with BRD7 interference using qRT-PCR and western blotting. CCK8 assay was used to examine the proliferation ability of MDA231 and MCF7 cells. Scratch wound healing assay was used to evaluate cell migration in MDA231 and MCF7 cells. Both Matrigel and three-dimensional invasion assays were performed to investigate the cell invasion ability after BRD7 overexpression or silencing or YB1 restoration in MDA231 and MCF7 cells. The potential interacting proteins of BRD7 were screened using co-immunoprecipitation combined with mass spectrometry and verified by co-immunoprecipitation in HEK293T cells. Additionally, we confirmed the specific binding region between BRD7 and YB1 in HEK293T cells by constructing a series of deletion mutants of BRD7 and YB1 respectively. Finally, xenograft and metastatic mouse models using MDA231 cells were established to confirm the effect of BRD7 on tumor growth and metastasis. Results Here, the results of a series of assays in vitro indicated that BRD7 has the ability to inhibit the mobility, migration and invasion of breast cancer cells. In addition, YB1 was identified as a novel interacting protein of BRD7, and BRD7 was found to associate with the C-terminus of YB1 via its N-terminus. BRD7 decreases the expression of YB1 through negatively regulating YB1 phosphorylation at Ser102, thereby promoting its proteasomal degradation. Furthermore, gene set enrichment analysis revealed that epithelial-mesenchymal transition (EMT) is the common change occurring with altered expression of either BRD7 or YB1 and that BRD7 represses mesenchymal genes and activates epithelial genes. Moreover, restoring the expression of YB1 antagonized the inhibitory effect of BRD7 on tumorigenicity, EMT, invasiveness and metastasis through a series of in vitro and in vivo experiments. Additionally, BRD7 expression was negatively correlated with the level of YB1 in breast cancer patients. The combination of low BRD7 and high YB1 expression was significantly associated with poor prognosis, distant metastasis and advanced TNM stage. Conclusions Collectively, these findings uncover that BRD7 blocks tumor growth, migration and metastasis by negatively regulating YB1-induced EMT, providing new insights into the mechanism by which BRD7 contributes to the progression and metastasis of breast cancer.https://doi.org/10.1186/s13046-019-1493-4Breast cancerBRD7YB1EMTInvasion and metastasis |
| spellingShingle | Weihong Niu Yanwei Luo Yao Zhou Mengna Li Chunchun Wu Yumei Duan Heran Wang Songqing Fan Zheng Li Wei Xiong Xiaoling Li Guiyuan Li Caiping Ren Hui Li Ming Zhou BRD7 suppresses invasion and metastasis in breast cancer by negatively regulating YB1-induced epithelial-mesenchymal transition Journal of Experimental & Clinical Cancer Research Breast cancer BRD7 YB1 EMT Invasion and metastasis |
| title | BRD7 suppresses invasion and metastasis in breast cancer by negatively regulating YB1-induced epithelial-mesenchymal transition |
| title_full | BRD7 suppresses invasion and metastasis in breast cancer by negatively regulating YB1-induced epithelial-mesenchymal transition |
| title_fullStr | BRD7 suppresses invasion and metastasis in breast cancer by negatively regulating YB1-induced epithelial-mesenchymal transition |
| title_full_unstemmed | BRD7 suppresses invasion and metastasis in breast cancer by negatively regulating YB1-induced epithelial-mesenchymal transition |
| title_short | BRD7 suppresses invasion and metastasis in breast cancer by negatively regulating YB1-induced epithelial-mesenchymal transition |
| title_sort | brd7 suppresses invasion and metastasis in breast cancer by negatively regulating yb1 induced epithelial mesenchymal transition |
| topic | Breast cancer BRD7 YB1 EMT Invasion and metastasis |
| url | https://doi.org/10.1186/s13046-019-1493-4 |
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