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...

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Autores principales:	Zhongwei Li, Diandian Wang, Xintian Chen, Wenwen Wang, Pengfei Wang, Pingfu Hou, Minle Li, Sufang Chu, Shuxi Qiao, Junnian Zheng, Jin Bai
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Cytology QH573-671
Acceso en línea:	https://doaj.org/article/10f93ae2b56e468c977ccd8ea25e918e
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spelling	oai:doaj.org-article:10f93ae2b56e468c977ccd8ea25e918e2021-11-14T12:06:52ZPRMT1-mediated EZH2 methylation promotes breast cancer cell proliferation and tumorigenesis10.1038/s41419-021-04381-52041-4889https://doaj.org/article/10f93ae2b56e468c977ccd8ea25e918e2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41419-021-04381-5https://doaj.org/toc/2041-4889Abstract 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.Zhongwei LiDiandian WangXintian ChenWenwen WangPengfei WangPingfu HouMinle LiSufang ChuShuxi QiaoJunnian ZhengJin BaiNature Publishing GrouparticleCytologyQH573-671ENCell Death and Disease, Vol 12, Iss 11, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cytology QH573-671
spellingShingle	Cytology QH573-671 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
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.
format	article
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
title	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_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_sort	prmt1-mediated ezh2 methylation promotes breast cancer cell proliferation and tumorigenesis
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/10f93ae2b56e468c977ccd8ea25e918e
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PRMT1-mediated EZH2 methylation promotes breast cancer cell proliferation and tumorigenesis

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