title: A central role for TRPS1 in the control of cell cycle and cancer development.
abstract: The eukaryotic cell cycle is controlled by a complex regulatory network, which is still poorly understood. Here we demonstrate that TRPS1, an atypical GATA factor, modulates cell proliferation and controls cell cycle progression. Silencing TRPS1 had a differential effect on the expression of nine key cell cycle-related genes. Eight of these genes are known to be involved in the regulation of the G2 phase and the G2/M transition of the cell cycle. Using cell synchronization studies, we confirmed that TRPS1 plays an important role in the control of cells in these phases of the cell cycle. We also show that silencing TRPS1 controls the expression of 53BP1, but not TP53. TRPS1 silencing also decreases the expression of two histone deacetylases, HDAC2 and HDAC4, as well as the overall HDAC activity in the cells, and leads to the subsequent increase in the acetylation of histone4 K16 but not of histone3 K9 or K18. Finally, we demonstrate that TRPS1 expression is elevated in luminal breast cancer cells and luminal breast cancer tissues as compared with other breast cancer subtypes. Overall, our study proposes that TRPS1 acts as a central hub in the control of cell cycle and proliferation during cancer development.
authors.affiliation: The Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Institute of Life Science, Southeast University, Nanjing, PR China. Contributed equally to this work.
authors.forename: Lele
authors.initials: L
authors.lastname: Wu
authors.affiliation: The Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Institute of Life Science, Southeast University, Nanjing, PR China. Contributed equally to this work.
authors.forename: Yuzhi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: The Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Institute of Life Science, Southeast University, Nanjing, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: The Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Institute of Life Science, Southeast University, Nanjing, PR China.
authors.forename: Shiyi
authors.initials: S
authors.lastname: Yu
authors.affiliation: The Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Institute of Life Science, Southeast University, Nanjing, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Xie
authors.affiliation: The Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Institute of Life Science, Southeast University, Nanjing, PR China.
authors.forename: Xingjuan
authors.initials: X
authors.lastname: Shi
authors.affiliation: Laboratory for Comparative Genomics and Bioinformatics and Jiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Qin
authors.affiliation: Laboratory for Comparative Genomics and Bioinformatics and Jiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Ma
authors.affiliation: Cancer Science Institute, National University of Singapore, 14 Medical Drive, Singapore.
authors.forename: Tuan Zea
authors.initials: TZ
authors.lastname: Tan
authors.affiliation: Cancer Science Institute, National University of Singapore, 14 Medical Drive, Singapore. Institute of Molecular and Cell Biology, A*STAR, 61 Biopolis Drive, Singapore. Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, Singapore.
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Thiery
authors.affiliation: The Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Institute of Life Science, Southeast University, Nanjing, PR China.
authors.forename: Liming
authors.initials: L
authors.lastname: Chen
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D002453:Cell Cycle / Q000235:genetics*; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000235:genetics*; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D047468:Immunoprecipitation; D020411:Oligonucleotide Array Sequence Analysis; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; D012097:Repressor Proteins; C108387:TRPS1 protein, human; D014157:Transcription Factors