Distinct Ring1b complexes defined by DEAD-box helicases and EMT transcription factors synergistically enhance E-cadherin silencing in breast cancer
Abstract Ring1b is a core subunit of polycomb repressive complex 1 (PRC1) and is essential in several high-risk cancers. However, the epigenetic mechanism of Ring1b underlying breast cancer malignancy is poorly understood. In this study, we showed increased expression of Ring1b promoted metastasis b...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2021-02-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-021-03491-4 |
| _version_ | 1818854170658078720 |
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| author | Yawei Wang Yingying Sun Chao Shang Lili Chen Hongyu Chen Dake Wang Xianlu Zeng |
| author_facet | Yawei Wang Yingying Sun Chao Shang Lili Chen Hongyu Chen Dake Wang Xianlu Zeng |
| author_sort | Yawei Wang |
| collection | DOAJ |
| description | Abstract Ring1b is a core subunit of polycomb repressive complex 1 (PRC1) and is essential in several high-risk cancers. However, the epigenetic mechanism of Ring1b underlying breast cancer malignancy is poorly understood. In this study, we showed increased expression of Ring1b promoted metastasis by weakening cell–cell adhesions of breast cancer cells. We confirmed that Ring1b could downregulate E-cadherin and contributed to an epigenetic rewiring via PRC1-dependent function by forming distinct complexes with DEAD-box RNA helicases (DDXs) or epithelial-mesenchymal transition transcription factors (EMT TFs) on site-specific loci of E-cadherin promoter. DDXs-Ring1b complexes moderately inhibited E-cadherin, which resulted in an early hybrid EMT state of epithelial cells, and EMT TFs-Ring1b complexes cooperated with DDXs-Ring1b complexes to further repress E-cadherin in mesenchymal-like cancer cells. Clinically, high expression of Ring1b with DDXs or EMT TFs predicted low levels of E-cadherin, metastatic behavior, and poor prognosis. These findings provide an epigenetic regulation mechanism of Ring1b complexes in E-cadherin expression. Ring1b complexes may be potential therapeutic targets and biomarkers for diagnosis and prognosis in invasion breast cancer. |
| first_indexed | 2024-12-19T07:48:27Z |
| format | Article |
| id | doaj.art-244d40385c1240bd8db99d18734644ce |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-12-19T07:48:27Z |
| publishDate | 2021-02-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-244d40385c1240bd8db99d18734644ce2022-12-21T20:30:14ZengNature Publishing GroupCell Death and Disease2041-48892021-02-0112211410.1038/s41419-021-03491-4Distinct Ring1b complexes defined by DEAD-box helicases and EMT transcription factors synergistically enhance E-cadherin silencing in breast cancerYawei Wang0Yingying Sun1Chao Shang2Lili Chen3Hongyu Chen4Dake Wang5Xianlu Zeng6The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Institute of Genetics and Cytology, Northeast Normal UniversityThe Key Laboratory of Molecular Epigenetics of the Ministry of Education, Institute of Genetics and Cytology, Northeast Normal UniversityThe Key Laboratory of Molecular Epigenetics of the Ministry of Education, Institute of Genetics and Cytology, Northeast Normal UniversityThe Key Laboratory of Molecular Epigenetics of the Ministry of Education, Institute of Genetics and Cytology, Northeast Normal UniversityThe Key Laboratory of Molecular Epigenetics of the Ministry of Education, Institute of Genetics and Cytology, Northeast Normal UniversityThe Key Laboratory of Molecular Epigenetics of the Ministry of Education, Institute of Genetics and Cytology, Northeast Normal UniversityThe Key Laboratory of Molecular Epigenetics of the Ministry of Education, Institute of Genetics and Cytology, Northeast Normal UniversityAbstract Ring1b is a core subunit of polycomb repressive complex 1 (PRC1) and is essential in several high-risk cancers. However, the epigenetic mechanism of Ring1b underlying breast cancer malignancy is poorly understood. In this study, we showed increased expression of Ring1b promoted metastasis by weakening cell–cell adhesions of breast cancer cells. We confirmed that Ring1b could downregulate E-cadherin and contributed to an epigenetic rewiring via PRC1-dependent function by forming distinct complexes with DEAD-box RNA helicases (DDXs) or epithelial-mesenchymal transition transcription factors (EMT TFs) on site-specific loci of E-cadherin promoter. DDXs-Ring1b complexes moderately inhibited E-cadherin, which resulted in an early hybrid EMT state of epithelial cells, and EMT TFs-Ring1b complexes cooperated with DDXs-Ring1b complexes to further repress E-cadherin in mesenchymal-like cancer cells. Clinically, high expression of Ring1b with DDXs or EMT TFs predicted low levels of E-cadherin, metastatic behavior, and poor prognosis. These findings provide an epigenetic regulation mechanism of Ring1b complexes in E-cadherin expression. Ring1b complexes may be potential therapeutic targets and biomarkers for diagnosis and prognosis in invasion breast cancer.https://doi.org/10.1038/s41419-021-03491-4 |
| spellingShingle | Yawei Wang Yingying Sun Chao Shang Lili Chen Hongyu Chen Dake Wang Xianlu Zeng Distinct Ring1b complexes defined by DEAD-box helicases and EMT transcription factors synergistically enhance E-cadherin silencing in breast cancer Cell Death and Disease |
| title | Distinct Ring1b complexes defined by DEAD-box helicases and EMT transcription factors synergistically enhance E-cadherin silencing in breast cancer |
| title_full | Distinct Ring1b complexes defined by DEAD-box helicases and EMT transcription factors synergistically enhance E-cadherin silencing in breast cancer |
| title_fullStr | Distinct Ring1b complexes defined by DEAD-box helicases and EMT transcription factors synergistically enhance E-cadherin silencing in breast cancer |
| title_full_unstemmed | Distinct Ring1b complexes defined by DEAD-box helicases and EMT transcription factors synergistically enhance E-cadherin silencing in breast cancer |
| title_short | Distinct Ring1b complexes defined by DEAD-box helicases and EMT transcription factors synergistically enhance E-cadherin silencing in breast cancer |
| title_sort | distinct ring1b complexes defined by dead box helicases and emt transcription factors synergistically enhance e cadherin silencing in breast cancer |
| url | https://doi.org/10.1038/s41419-021-03491-4 |
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