PRMT1-mediated EZH2 methylation promotes breast cancer cell proliferation and tumorigenesis
Abstract Protein arginine methyltransferase 1 (PRMT1) is able to promote breast cancer cell proliferation. However, the detailed mechanisms of PRMT1-mediated breast cancer cell proliferation are largely unknown. In this study, we reveal that PRMT1-mediated methylation of EZH2 at the R342 site (meR34...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2021-11-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-021-04381-5 |
| _version_ | 1818932860757737472 |
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| author | Zhongwei Li Diandian Wang Xintian Chen Wenwen Wang Pengfei Wang Pingfu Hou Minle Li Sufang Chu Shuxi Qiao Junnian Zheng Jin Bai |
| author_facet | Zhongwei Li Diandian Wang Xintian Chen Wenwen Wang Pengfei Wang Pingfu Hou Minle Li Sufang Chu Shuxi Qiao Junnian Zheng Jin Bai |
| author_sort | Zhongwei Li |
| collection | DOAJ |
| description | Abstract Protein arginine methyltransferase 1 (PRMT1) is able to promote breast cancer cell proliferation. However, the detailed mechanisms of PRMT1-mediated breast cancer cell proliferation are largely unknown. In this study, we reveal that PRMT1-mediated methylation of EZH2 at the R342 site (meR342-EZH2) has a great effect on PRMT1-induced cell proliferation. We also demonstrate that meR342-EZH2 can accelerate breast cancer cell proliferation in vitro and in vivo. Further, we show that meR342-EZH2 promotes cell cycle progression by repressing P16 and P21 transcription expression. In terms of mechanism, we illustrate that meR342-EZH2 facilitates EZH2 binding with SUZ12 and PRC2 assembly by preventing AMPKα1-mediated phosphorylation of pT311-EZH2, which results in suppression of P16 and P21 transcription by enhancing EZH2 expression and H3K27me3 enrichment at P16 and P21 promoters. Finally, we validate that the expression of PRMT1 and meR342-EZH2 is negatively correlated with pT311-EZH2 expression. Our findings suggest that meR342-EZH2 may become a novel therapeutic target for the treatment of breast cancer. |
| first_indexed | 2024-12-20T04:39:12Z |
| format | Article |
| id | doaj.art-10f93ae2b56e468c977ccd8ea25e918e |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-12-20T04:39:12Z |
| publishDate | 2021-11-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-10f93ae2b56e468c977ccd8ea25e918e2022-12-21T19:53:10ZengNature Publishing GroupCell Death and Disease2041-48892021-11-01121111110.1038/s41419-021-04381-5PRMT1-mediated EZH2 methylation promotes breast cancer cell proliferation and tumorigenesisZhongwei Li0Diandian Wang1Xintian Chen2Wenwen Wang3Pengfei Wang4Pingfu Hou5Minle Li6Sufang Chu7Shuxi Qiao8Junnian Zheng9Jin Bai10Cancer Institute, Xuzhou Medical UniversityCancer Institute, Xuzhou Medical UniversityCancer Institute, Xuzhou Medical UniversityCancer Institute, Xuzhou Medical UniversityCancer Institute, Xuzhou Medical UniversityCancer Institute, Xuzhou Medical UniversityCancer Institute, Xuzhou Medical UniversityCancer Institute, Xuzhou Medical UniversityCancer Institute, Xuzhou Medical UniversityCancer Institute, Xuzhou Medical UniversityCancer Institute, Xuzhou Medical UniversityAbstract Protein arginine methyltransferase 1 (PRMT1) is able to promote breast cancer cell proliferation. However, the detailed mechanisms of PRMT1-mediated breast cancer cell proliferation are largely unknown. In this study, we reveal that PRMT1-mediated methylation of EZH2 at the R342 site (meR342-EZH2) has a great effect on PRMT1-induced cell proliferation. We also demonstrate that meR342-EZH2 can accelerate breast cancer cell proliferation in vitro and in vivo. Further, we show that meR342-EZH2 promotes cell cycle progression by repressing P16 and P21 transcription expression. In terms of mechanism, we illustrate that meR342-EZH2 facilitates EZH2 binding with SUZ12 and PRC2 assembly by preventing AMPKα1-mediated phosphorylation of pT311-EZH2, which results in suppression of P16 and P21 transcription by enhancing EZH2 expression and H3K27me3 enrichment at P16 and P21 promoters. Finally, we validate that the expression of PRMT1 and meR342-EZH2 is negatively correlated with pT311-EZH2 expression. Our findings suggest that meR342-EZH2 may become a novel therapeutic target for the treatment of breast cancer.https://doi.org/10.1038/s41419-021-04381-5 |
| spellingShingle | Zhongwei Li Diandian Wang Xintian Chen Wenwen Wang Pengfei Wang Pingfu Hou Minle Li Sufang Chu Shuxi Qiao Junnian Zheng Jin Bai PRMT1-mediated EZH2 methylation promotes breast cancer cell proliferation and tumorigenesis Cell Death and Disease |
| title | PRMT1-mediated EZH2 methylation promotes breast cancer cell proliferation and tumorigenesis |
| title_full | PRMT1-mediated EZH2 methylation promotes breast cancer cell proliferation and tumorigenesis |
| title_fullStr | PRMT1-mediated EZH2 methylation promotes breast cancer cell proliferation and tumorigenesis |
| title_full_unstemmed | PRMT1-mediated EZH2 methylation promotes breast cancer cell proliferation and tumorigenesis |
| title_short | PRMT1-mediated EZH2 methylation promotes breast cancer cell proliferation and tumorigenesis |
| title_sort | prmt1 mediated ezh2 methylation promotes breast cancer cell proliferation and tumorigenesis |
| url | https://doi.org/10.1038/s41419-021-04381-5 |
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