title: The dual function of PRMT1 in modulating epithelial-mesenchymal transition and cellular senescence in breast cancer cells through regulation of ZEB1.
abstract: Although the involvement of protein arginine methyltransferase 1 (PRMT1) in tumorigenesis has been reported, its roles in breast cancer progression and metastasis has not been elucidated. Here we identified PRMT1 as a key regulator of the epithelial-mesenchymal transition (EMT) in breast cancer. We showed that the EMT program induced by PRMT1 endowed the human mammary epithelial cells with cancer stem cell properties. Moreover, PRMT1 promoted the migratory and invasive behaviors in breast cancer cells. We also demonstrated that abrogation of PRMT1 expression in breast cancer cells abated metastasis in vivo in mouse model. In addition, knockdown of PRMT1 arrested cell growth in G1 tetraploidy and induced cellular senescence. Mechanistically, PRMT1 impacted EMT process and cellular senescence by mediating the asymmetric dimethylation of arginine 3 of histone H4 (H4R3me2as) at the ZEB1 promoter to activate its transcription, indicating the essential roles of this epigenetic control both in EMT and in senescence. Thus, we unraveled a dual function of PRMT1 in modulation of both EMT and senescence via regulating ZEB1. This finding points to the potent value of PRMT1 as a dual therapeutic target for preventing metastasis and for inhibiting cancer cell growth in malignant breast cancer patients.
authors.affiliation: The Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun 130021, China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: The Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China.
authors.forename: Juechao
authors.initials: J
authors.lastname: Zhang
authors.affiliation: The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun 130021, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Lu
authors.affiliation: The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun 130021, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun 130021, China.
authors.forename: Pengyu
authors.initials: P
authors.lastname: Geng
authors.affiliation: The Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China.
authors.forename: Baiqu
authors.initials: B
authors.lastname: Huang
authors.affiliation: The Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun 130021, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D016922:Cellular Senescence / Q000235:genetics*; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006657:Histones; D006801:Humans; D051379:Mice; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D057891:Tetraploidy; D000071799:Zinc Finger E-box-Binding Homeobox 1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D006657:Histones; D012097:Repressor Proteins; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; C099988:PRMT1 protein, human; D011484:Protein-Arginine N-Methyltransferases
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