title: Histone methyltransferase SMYD3 promotes MRTF-A-mediated transactivation of MYL9 and migration of MCF-7 breast cancer cells.
abstract: Myocardin-related transcription factor-A (MRTF-A) is a Rho signal-responsive transcriptional coactivator of serum response factor (SRF). Recent studies indicated that MRTF-A might be an important regulator of mammary gland and be involved in cancer metastasis. However, the roles of histone modification in the MRTF-A-dependent signal pathway and tumor migration are still not very clear. Here, we report that histone methylation is required for the MRTF-A-mediated upregulation of myosin regulatory light chain 9 (MYL9), an important cytoskeletal component which is implicated in cell migration. Furthermore, we demonstrate that SET and MYND domain containing protein 3 (SMYD3), a hitone methyltransferase (HMT) associated with carcinogenesis, might be the one which is responsible for the histone methylation occurred in the MRTF-A-mediated- transactivation of MYL9 and migration of breast cancer cells. Overexpression of SMYD3 promotes MRTF-A-mediated upregulation of MYL9 and migration of MCF-7 breast cancer cells, while contrary results were observed when the endogenous MRTF-A and SMYD3 were suppressed with specific siRNAs. In addition, the mutation analysis suggested that this cooperative transactivation is mainly mediated via the proximal binding element of MRTF-A in the promoter of MYL9, and the HMT activity of SMYD3 is required as well. Our findings reveal a new mechanism by which MRTF-A and SMYD3 functions in transcriptional regulation and cell migration, and provide a better understanding for metastasis of breast cancer.
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China; Tianjin Key Laboratory of Industrial Microbiology, Tianjin 300457, China. Electronic address: luoxuegangcn@gmail.com.
authors.forename: Xue-Gang
authors.initials: XG
authors.lastname: Luo
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China; Tianjin Key Laboratory of Industrial Microbiology, Tianjin 300457, China.
authors.forename: Chun-Ling
authors.initials: CL
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China; Tianjin Key Laboratory of Industrial Microbiology, Tianjin 300457, China.
authors.forename: Wen-Wen
authors.initials: WW
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China; Tianjin Key Laboratory of Industrial Microbiology, Tianjin 300457, China.
authors.forename: Zhi-Peng
authors.initials: ZP
authors.lastname: Liu
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China; Tianjin Key Laboratory of Industrial Microbiology, Tianjin 300457, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China; Tianjin Key Laboratory of Industrial Microbiology, Tianjin 300457, China.
authors.forename: Ai
authors.initials: A
authors.lastname: Mu
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China; Tianjin Key Laboratory of Industrial Microbiology, Tianjin 300457, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Guo
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China; Tianjin Key Laboratory of Industrial Microbiology, Tianjin 300457, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China; Tianjin Key Laboratory of Industrial Microbiology, Tianjin 300457, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China; Tianjin Key Laboratory of Industrial Microbiology, Tianjin 300457, China; School of Medicine, Wuhan University of Science and Technology, Wuhan 430081, China. Electronic address: tony@tust.edu.cn.
authors.forename: Tong-Cun
authors.initials: TC
authors.lastname: Zhang
mesh_terms: D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement; D004268:DNA-Binding Proteins / Q000378:metabolism*; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D061986:MCF-7 Cells; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000378:metabolism*; D015514:Oncogene Proteins, Fusion / Q000378:metabolism*; D000071156:Promyelocytic Leukemia Protein; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C431575:MRTFA protein, human; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D000071156:Promyelocytic Leukemia Protein; D034741:RNA, Small Interfering; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; D011495:Histone-Lysine N-Methyltransferase; C506278:SMYD3 protein, human
keywords: Breast cancer; Cell migration; Histone methylation; MRTF-A; MYL9; SMYD3; Transactivation