title: PRMT7 induces epithelial-to-mesenchymal transition and promotes metastasis in breast cancer.
abstract: Epithelial-to-mesenchymal transition (EMT) enables metastasis. E-cadherin loss is a hallmark of EMT, but there remains an incomplete understanding of the epigenetics of this process. The protein arginine methyltransferase PRMT7 functions in various physiologic processes, including mRNA splicing, DNA repair, and neural differentiation, but its possible roles in cancer and metastasis have not been explored. In this report, we show that PRMT7 is expressed at higher levels in breast carcinoma cells and that elevated PRMT7 mediates EMT and metastasis. PRMT7 could inhibit the expression of E-cadherin by binding to its proximal promoter in a manner associated with altered histone methylation, specifically with elevated H4R3me2s and reduced H3K4me3, H3Ac, and H4Ac, which occurred at the E-cadherin promoter upon EMT induction. Moreover, PRMT7 interacted with YY1 and HDAC3 and was essential to link these proteins to the E-cadherin promoter. Silencing PRMT7 restored E-cadherin expression by repressing H4R3me2s and by increasing H3K4me3 and H4Ac, attenuating cell migration and invasion in MDA-MB-231 breast cancer cells. Overall, our results define PRMT7 as an inducer of breast cancer metastasis and present the opportunity for applying PRMT7-targeted therapeutics to treat highly invasive breast cancers.
authors.affiliation: The Key Laboratory of Molecular Epigenetics of Ministry of Education, Northeast Normal University, Changchun, China.
authors.forename: Ruosi
authors.initials: R
authors.lastname: Yao
authors.affiliation: The Institute of Genetics and Cytology, Northeast Normal University, Changchun, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Jiang
authors.affiliation: The Key Laboratory of Molecular Epigenetics of Ministry of Education, Northeast Normal University, Changchun, China.
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Pathology, China-Japan Union Hospital of Jilin University, Changchun, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.affiliation: The Institute of Genetics and Cytology, Northeast Normal University, Changchun, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: The Institute of Genetics and Cytology, Northeast Normal University, Changchun, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Du
authors.affiliation: The Key Laboratory of Molecular Epigenetics of Ministry of Education, Northeast Normal University, Changchun, China.
authors.forename: Pingfu
authors.initials: P
authors.lastname: Hou
authors.affiliation: The Institute of Genetics and Cytology, Northeast Normal University, Changchun, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: The Key Laboratory of Molecular Epigenetics of Ministry of Education, Northeast Normal University, Changchun, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun, China.
authors.forename: Guannan
authors.initials: G
authors.lastname: Wang
authors.affiliation: The Institute of Genetics and Cytology, Northeast Normal University, Changchun, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The Liggins Institute, the University of Auckland, Auckland, New Zealand.
authors.forename: Dong-Xu
authors.initials: DX
authors.lastname: Liu
authors.affiliation: The Key Laboratory of Molecular Epigenetics of Ministry of Education, Northeast Normal University, Changchun, China. luj809@nenu.edu.cn huangbq705@nenu.edu.cn.
authors.forename: Baiqu
authors.initials: B
authors.lastname: Huang
authors.affiliation: The Institute of Genetics and Cytology, Northeast Normal University, Changchun, China. luj809@nenu.edu.cn huangbq705@nenu.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D011484:Protein-Arginine N-Methyltransferases / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C487994:PRMT7 protein, human; D011484:Protein-Arginine N-Methyltransferases