PRMT1-mediated EZH2 methylation promotes breast cancer cell proliferation and tumorigenesis

• Published in: Cell death & disease Vol. 12; no. 11; pp. 1080 - 11
• Main Authors: Li, Zhongwei, Wang, Diandian, Chen, Xintian, Wang, Wenwen, Wang, Pengfei, Hou, Pingfu, Li, Minle, Chu, Sufang, Qiao, Shuxi, Zheng, Junnian, Bai, Jin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13.11.2021; Springer Nature B.V; Nature Publishing Group
• Subjects: 13/1; 13/31; 13/95; 38/90; 42; 631/337/458/1648; 631/337/458/1733; 631/67/1059/602; 631/67/1347; 631/80/83; 64/60; 82/51; Animals; Antibodies; Biochemistry; Biomedical and Life Sciences; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Carcinogenesis; Cell Biology; Cell Culture; Cell cycle; Cell growth; Cell Line, Tumor; Cell Proliferation; Cyclin-dependent kinase inhibitor p21; Enhancer of Zeste Homolog 2 Protein - metabolism; Female; Humans; Immunology; Kinases; Life Sciences; Methylation; Mice; Mice, Nude; Phosphorylation; Protein arginine methyltransferase; Protein-Arginine N-Methyltransferases - metabolism; Transcription; Tumorigenesis
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-021-04381-5

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.