RNF20 Is Critical for Snail-Mediated E-Cadherin Repression in Human Breast Cancer
BackgroundE-cadherin, a hallmark of epithelial-mesenchymal transition (EMT), is often repressed due to Snail-mediated epigenetic modification; however, the exact mechanism remains unclear. There is an urgent need to understand the determinants of tumor aggressiveness and identify potential therapeut...
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Frontiers Media S.A.
2020-12-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2020.613470/full |
| _version_ | 1818387027629965312 |
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| author | Danping Wang Danping Wang Yifan Wang Yifan Wang Yifan Wang Xuebiao Wu Xiangxing Kong Jun Li Chenfang Dong Chenfang Dong Chenfang Dong |
| author_facet | Danping Wang Danping Wang Yifan Wang Yifan Wang Yifan Wang Xuebiao Wu Xiangxing Kong Jun Li Chenfang Dong Chenfang Dong Chenfang Dong |
| author_sort | Danping Wang |
| collection | DOAJ |
| description | BackgroundE-cadherin, a hallmark of epithelial-mesenchymal transition (EMT), is often repressed due to Snail-mediated epigenetic modification; however, the exact mechanism remains unclear. There is an urgent need to understand the determinants of tumor aggressiveness and identify potential therapeutic targets in breast cancer.Experimental designWe studied the association of RNF20 with Snail and G9a by co-immunoprecipitation. We employed quantitative real-time PCR, ChIP, transwell assay, colony formation assay, and mammosphere assay to dissect the molecular events associated with the repression of E-cadherin in human breast cancer. We used a proteogenomic dataset that contains 105 breast tumor samples to determine the clinical relevance of RNF20 by Kaplan-Meier analyses.ResultsIn this study, we identified that Snail interacted with RNF20, an E3 ubiquitin-protein ligase responsible for monoubiquitination of H2BK120, and G9a, a methyltransferase for H3K9me2. RNF20 expression led to the inhibition of E-cadherin expression in the human breast cancer cells. Mechanically, we showed that RNF20 and H3K9m2 were enriched on the promoter of E-cadherin and knockdown of Snail reduced the enrichment of RNF20, showing a Snail-dependent manner. RNF20 expression enhanced breast cancer cell migration, invasion, tumorsphere and colony formation. Clinically, patients with high RNF20 expression had shorter overall survival.ConclusionRNF20 expression contributes to EMT induction and breast cancer progression through Snail-mediated epigenetic suppression of E-cadherin expression, suggesting the importance of RNF20 in breast cancer. |
| first_indexed | 2024-12-14T04:03:25Z |
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| id | doaj.art-11dc1ae6fe3d4e68b282a095a7b69f3e |
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| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-14T04:03:25Z |
| publishDate | 2020-12-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj.art-11dc1ae6fe3d4e68b282a095a7b69f3e2022-12-21T23:17:53ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-12-011010.3389/fonc.2020.613470613470RNF20 Is Critical for Snail-Mediated E-Cadherin Repression in Human Breast CancerDanping Wang0Danping Wang1Yifan Wang2Yifan Wang3Yifan Wang4Xuebiao Wu5Xiangxing Kong6Jun Li7Chenfang Dong8Chenfang Dong9Chenfang Dong10Department of Pathology and Pathophysiology, and Department of Surgical Oncology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaKey Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Pathology and Pathophysiology, and Department of Surgical Oncology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaKey Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, ChinaCancer Institute of Integrative Medicine, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, ChinaDepartment of Pathophysiology, Zunyi Medical University, Zunyi, ChinaDepartment of Pathology and Pathophysiology, and Department of Surgical Oncology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Pathology and Pathophysiology, and Department of Surgical Oncology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Pathology and Pathophysiology, and Department of Surgical Oncology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaKey Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Pathophysiology, Zunyi Medical University, Zunyi, ChinaBackgroundE-cadherin, a hallmark of epithelial-mesenchymal transition (EMT), is often repressed due to Snail-mediated epigenetic modification; however, the exact mechanism remains unclear. There is an urgent need to understand the determinants of tumor aggressiveness and identify potential therapeutic targets in breast cancer.Experimental designWe studied the association of RNF20 with Snail and G9a by co-immunoprecipitation. We employed quantitative real-time PCR, ChIP, transwell assay, colony formation assay, and mammosphere assay to dissect the molecular events associated with the repression of E-cadherin in human breast cancer. We used a proteogenomic dataset that contains 105 breast tumor samples to determine the clinical relevance of RNF20 by Kaplan-Meier analyses.ResultsIn this study, we identified that Snail interacted with RNF20, an E3 ubiquitin-protein ligase responsible for monoubiquitination of H2BK120, and G9a, a methyltransferase for H3K9me2. RNF20 expression led to the inhibition of E-cadherin expression in the human breast cancer cells. Mechanically, we showed that RNF20 and H3K9m2 were enriched on the promoter of E-cadherin and knockdown of Snail reduced the enrichment of RNF20, showing a Snail-dependent manner. RNF20 expression enhanced breast cancer cell migration, invasion, tumorsphere and colony formation. Clinically, patients with high RNF20 expression had shorter overall survival.ConclusionRNF20 expression contributes to EMT induction and breast cancer progression through Snail-mediated epigenetic suppression of E-cadherin expression, suggesting the importance of RNF20 in breast cancer.https://www.frontiersin.org/articles/10.3389/fonc.2020.613470/fullepithelial-mesenchymal transitionsnailRNF20ubiquitinationG9a |
| spellingShingle | Danping Wang Danping Wang Yifan Wang Yifan Wang Yifan Wang Xuebiao Wu Xiangxing Kong Jun Li Chenfang Dong Chenfang Dong Chenfang Dong RNF20 Is Critical for Snail-Mediated E-Cadherin Repression in Human Breast Cancer Frontiers in Oncology epithelial-mesenchymal transition snail RNF20 ubiquitination G9a |
| title | RNF20 Is Critical for Snail-Mediated E-Cadherin Repression in Human Breast Cancer |
| title_full | RNF20 Is Critical for Snail-Mediated E-Cadherin Repression in Human Breast Cancer |
| title_fullStr | RNF20 Is Critical for Snail-Mediated E-Cadherin Repression in Human Breast Cancer |
| title_full_unstemmed | RNF20 Is Critical for Snail-Mediated E-Cadherin Repression in Human Breast Cancer |
| title_short | RNF20 Is Critical for Snail-Mediated E-Cadherin Repression in Human Breast Cancer |
| title_sort | rnf20 is critical for snail mediated e cadherin repression in human breast cancer |
| topic | epithelial-mesenchymal transition snail RNF20 ubiquitination G9a |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2020.613470/full |
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