Protein arginine methyltransferases (PRMTs) catalyze protein arginine methylation and are linked to carcinogenesis and metastasis. Some members of PRMTs have been found to undergo automethylation; however, the biologic significance of this self-modification is not entirely clear. In this report, we demonstrate that R531 of PRMT7 is self-methylated, both in vitro and in vivo. Automethylation of PRMT7 plays a key role in inducing the epithelial-mesenchymal transition (EMT) program and in promoting the migratory and invasive behavior of breast cancer cells. We also prove in a nude mouse model that expression of wild-type PRMT7 in MCF7 breast cancer cells promotes metastasis in vivo, in contrast to the PRMT7 R531K mutant (a mimic of the unmethylated status). Moreover, our immunohistochemical data unravel a close link between PRMT7 automethylation and the clinical outcome of breast carcinomas. Mechanistically, we determine that loss of PRMT7 automethylation leads to the reduction of its recruitment to the E-cadherin promoter by YY1, which consequently derepresses the E-cadherin expression through decreasing the H4R3me2s level. The findings in this work define a novel post-translational modification of PRMT7 that has a promoting impacton breast cancer metastasis.
[1]Northeast Normal Univ, Inst Genet & Cytol, 5268 Renmin St, Changchun 130024, Peoples R China.
[2]Northeast Normal Univ, Key Lab Mol Epigenet, Minist Educ, Changchun, Peoples R China.
[3]Northeast Normal Univ, Natl Engn Lab Druggable Gene & Prot Screening, Changchun, Peoples R China.
[4]Jilin Univ, Hosp 1, Pathol Diagnost Ctr, Changchun, Peoples R China.
[5]Auckland Univ Technol, Sch Sci, Fac Hlth & Environm Sci, Auckland, New Zealand.
(8.0+极速模式)