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FASEB J. 2017 Jun;31(6):2287-2300. doi: 10.1096/fj.201601196R. Epub 2017 Feb 10.

Automethylation of protein arginine methyltransferase 7 and its impact on breast cancer progression.

Author information

1
The Institute of Genetics and Cytology, Northeast Normal University, Changchun, China.
2
The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun, China.
3
Pathological Diagnostic Center, The First Hospital of Jilin University, Changchun, China.
4
National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun, China; and.
5
School of Science, Faculty of Health and Environmental Sciences, Auckland University of Technology, Auckland, New Zealand.
6
The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun, China; huangbq705@nenu.edu.cn.
7
The Institute of Genetics and Cytology, Northeast Normal University, Changchun, China; luj809@nenu.edu.cn.

Abstract

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 impact on breast cancer metastasis.-Geng, P., Zhang, Y., Liu, X., Zhang, N., Liu, Y., Liu, X., Lin, C., Yan, X., Li, Z., Wang, G., Li, Y., Tan, J., Liu, D.-X., Huang, B., Lu, J. Automethylation of protein arginine methyltransferase 7 and its impact on breast cancer progression.

KEYWORDS:

E-cadherin; YY1; invasion; migration

PMID:
28188177
DOI:
10.1096/fj.201601196R
[Indexed for MEDLINE]

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