Methylation of ESR1 promoter induced by SNAI2–DNMT3B complex promotes epithelial–mesenchymal transition and correlates with poor prognosis in ERα‐positive breast cancers
Abstract Estrogen receptor α (ERα) serves as an essential therapeutic predictor for breast cancer (BC) patients and is regulated by epigenetic modification. Abnormal methylation of cytosine phosphoric acid guanine islands in the estrogen receptor 1 (ESR1) gene promoter could silence or decrease ERα...
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| Format: | Article |
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Wiley
2023-12-01
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| Series: | MedComm |
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| Online Access: | https://doi.org/10.1002/mco2.403 |
| _version_ | 1797373573295243264 |
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| author | Ji‐Wei Li Qiu‐Min Deng Jian‐Ling Zhu Wei Min Xiao‐Yi Hu Hong‐ Yu Chen Zhong Luo Lin‐Ling Lin Xiao‐Long Wei Yong‐Qu Zhang Kang‐Liang Lou Yi‐Yang Gao Guo‐Jun Zhang Jing‐Wen Bai |
| author_facet | Ji‐Wei Li Qiu‐Min Deng Jian‐Ling Zhu Wei Min Xiao‐Yi Hu Hong‐ Yu Chen Zhong Luo Lin‐Ling Lin Xiao‐Long Wei Yong‐Qu Zhang Kang‐Liang Lou Yi‐Yang Gao Guo‐Jun Zhang Jing‐Wen Bai |
| author_sort | Ji‐Wei Li |
| collection | DOAJ |
| description | Abstract Estrogen receptor α (ERα) serves as an essential therapeutic predictor for breast cancer (BC) patients and is regulated by epigenetic modification. Abnormal methylation of cytosine phosphoric acid guanine islands in the estrogen receptor 1 (ESR1) gene promoter could silence or decrease ERα expression. In ERα‐negative BC, we previously found snail family transcriptional repressor 2 (SNAI2), a zinc‐finger transcriptional factor, recruited lysine‐specific demethylase 1 to the promoter to transcriptionally suppress ERα expression by demethylating histone H3 lysine 4 dimethylation (H3K4me2). However, the role of SNAI2 in ERα‐positive BC remains elusive. In this study, we observed a positive correlation between SNAI2 and ESR1 methylation, and SNAI2 promoted ESR1 methylation by recruiting DNA methyltransferase 3 beta (DNMT3B) rather than DNA methyltransferase 1 (DNMT1) in ERα‐positive BC cells. Subsequent enrichment analysis illustrated that ESR1 methylation is strongly correlated with cell adhesion and junction. Knocking down DNMT3B could partially reverse SNAI2 overexpression‐induced cell proliferation, migration, and invasion. Moreover, high DNMT3B expression predicted poor relapse‐free survival and overall survival in ERα‐positive BC patients. In conclusion, this study demonstrated the novel mechanisms of the ESR1 methylation mediated with the SNAI2/DNMT3B complex and enhanced awareness of ESR1 methylation's role in promoting epithelial–mesenchymal transition in BC. |
| first_indexed | 2024-03-08T18:52:27Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2688-2663 |
| language | English |
| last_indexed | 2024-03-08T18:52:27Z |
| publishDate | 2023-12-01 |
| publisher | Wiley |
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| series | MedComm |
| spelling | doaj.art-d782978519d347b0ad247158a9f01a0d2023-12-28T16:52:34ZengWileyMedComm2688-26632023-12-0146n/an/a10.1002/mco2.403Methylation of ESR1 promoter induced by SNAI2–DNMT3B complex promotes epithelial–mesenchymal transition and correlates with poor prognosis in ERα‐positive breast cancersJi‐Wei Li0Qiu‐Min Deng1Jian‐Ling Zhu2Wei Min3Xiao‐Yi Hu4Hong‐ Yu Chen5Zhong Luo6Lin‐Ling Lin7Xiao‐Long Wei8Yong‐Qu Zhang9Kang‐Liang Lou10Yi‐Yang Gao11Guo‐Jun Zhang12Jing‐Wen Bai13Fujian Key Laboratory of Precision Diagnosis and Treatment in Breast CancerXiang'an Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen P. R. ChinaFujian Key Laboratory of Precision Diagnosis and Treatment in Breast CancerXiang'an Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen P. R. ChinaDepartment of PathologyCancer Hospital of Shantou University Medical CollegeShantouP. R. ChinaFujian Key Laboratory of Precision Diagnosis and Treatment in Breast CancerXiang'an Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen P. R. ChinaDepartment of Respiratory, Critical Care and Sleep MedicineXiang'an Hospital of Xiamen University, School of Medicine, Xiamen UniversityXiamenP. R. ChinaFujian Key Laboratory of Precision Diagnosis and Treatment in Breast CancerXiang'an Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen P. R. ChinaFujian Key Laboratory of Precision Diagnosis and Treatment in Breast CancerXiang'an Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen P. R. ChinaFujian Key Laboratory of Precision Diagnosis and Treatment in Breast CancerXiang'an Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen P. R. ChinaDepartment of PathologyCancer Hospital of Shantou University Medical CollegeShantouP. R. ChinaFujian Key Laboratory of Precision Diagnosis and Treatment in Breast CancerXiang'an Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen P. R. ChinaFujian Key Laboratory of Precision Diagnosis and Treatment in Breast CancerXiang'an Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen P. R. ChinaFujian Key Laboratory of Precision Diagnosis and Treatment in Breast CancerXiang'an Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen P. R. ChinaFujian Key Laboratory of Precision Diagnosis and Treatment in Breast CancerXiang'an Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen P. R. ChinaFujian Key Laboratory of Precision Diagnosis and Treatment in Breast CancerXiang'an Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen P. R. ChinaAbstract Estrogen receptor α (ERα) serves as an essential therapeutic predictor for breast cancer (BC) patients and is regulated by epigenetic modification. Abnormal methylation of cytosine phosphoric acid guanine islands in the estrogen receptor 1 (ESR1) gene promoter could silence or decrease ERα expression. In ERα‐negative BC, we previously found snail family transcriptional repressor 2 (SNAI2), a zinc‐finger transcriptional factor, recruited lysine‐specific demethylase 1 to the promoter to transcriptionally suppress ERα expression by demethylating histone H3 lysine 4 dimethylation (H3K4me2). However, the role of SNAI2 in ERα‐positive BC remains elusive. In this study, we observed a positive correlation between SNAI2 and ESR1 methylation, and SNAI2 promoted ESR1 methylation by recruiting DNA methyltransferase 3 beta (DNMT3B) rather than DNA methyltransferase 1 (DNMT1) in ERα‐positive BC cells. Subsequent enrichment analysis illustrated that ESR1 methylation is strongly correlated with cell adhesion and junction. Knocking down DNMT3B could partially reverse SNAI2 overexpression‐induced cell proliferation, migration, and invasion. Moreover, high DNMT3B expression predicted poor relapse‐free survival and overall survival in ERα‐positive BC patients. In conclusion, this study demonstrated the novel mechanisms of the ESR1 methylation mediated with the SNAI2/DNMT3B complex and enhanced awareness of ESR1 methylation's role in promoting epithelial–mesenchymal transition in BC.https://doi.org/10.1002/mco2.403breast cancerDNA methyltransferase 3 betaepithelial–mesenchymal transitionESR1 methylationsnail family transcriptional repressor 2 |
| spellingShingle | Ji‐Wei Li Qiu‐Min Deng Jian‐Ling Zhu Wei Min Xiao‐Yi Hu Hong‐ Yu Chen Zhong Luo Lin‐Ling Lin Xiao‐Long Wei Yong‐Qu Zhang Kang‐Liang Lou Yi‐Yang Gao Guo‐Jun Zhang Jing‐Wen Bai Methylation of ESR1 promoter induced by SNAI2–DNMT3B complex promotes epithelial–mesenchymal transition and correlates with poor prognosis in ERα‐positive breast cancers MedComm breast cancer DNA methyltransferase 3 beta epithelial–mesenchymal transition ESR1 methylation snail family transcriptional repressor 2 |
| title | Methylation of ESR1 promoter induced by SNAI2–DNMT3B complex promotes epithelial–mesenchymal transition and correlates with poor prognosis in ERα‐positive breast cancers |
| title_full | Methylation of ESR1 promoter induced by SNAI2–DNMT3B complex promotes epithelial–mesenchymal transition and correlates with poor prognosis in ERα‐positive breast cancers |
| title_fullStr | Methylation of ESR1 promoter induced by SNAI2–DNMT3B complex promotes epithelial–mesenchymal transition and correlates with poor prognosis in ERα‐positive breast cancers |
| title_full_unstemmed | Methylation of ESR1 promoter induced by SNAI2–DNMT3B complex promotes epithelial–mesenchymal transition and correlates with poor prognosis in ERα‐positive breast cancers |
| title_short | Methylation of ESR1 promoter induced by SNAI2–DNMT3B complex promotes epithelial–mesenchymal transition and correlates with poor prognosis in ERα‐positive breast cancers |
| title_sort | methylation of esr1 promoter induced by snai2 dnmt3b complex promotes epithelial mesenchymal transition and correlates with poor prognosis in erα positive breast cancers |
| topic | breast cancer DNA methyltransferase 3 beta epithelial–mesenchymal transition ESR1 methylation snail family transcriptional repressor 2 |
| url | https://doi.org/10.1002/mco2.403 |
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