title: SETDB1 mediated FosB expression increases the cell proliferation rate during anticancer drug therapy.
abstract: The efficacy of anticancer drugs depends on a variety of signaling pathways, which can be positively or negatively regulated. In this study, we show that SETDB1 HMTase is down-regulated at the transcriptional level by several anticancer drugs, due to its inherent instability. Using RNA sequence analysis, we identified FosB as being regulated by SETDB1 during anticancer drug therapy. FosB expression was increased by treatment with doxorubicin, taxol and siSETDB1. Moreover, FosB was associated with an increased rate of proliferation. Combinatory transfection of siFosB and siSETDB1 was slightly increased compared to transfection of siFosB. Furthermore, FosB was regulated by multiple kinase pathways. ChIP analysis showed that SETDB1 and H3K9me3 interact with a specific region of the FosB promoter. These results suggest that SETDB1- mediated FosB expression is a common molecular phenomenon, and might be a novel pathway responsible for the increase in cell proliferation that frequently occurs during anticancer drug therapy. [BMB Reports 2016; 49(4): 238-243].
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Kangwon National University, Chuncheon 24341, Korea.
authors.forename: Han-Heom
authors.initials: HH
authors.lastname: Na
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Kangwon National University, Chuncheon 24341, Korea.
authors.forename: Hee-Jung
authors.initials: HJ
authors.lastname: Noh
authors.affiliation: Division of Respiratory Viruses, Center for Disease Control and Prevention, Korea National Institute of Health, Osong 28160, Korea.
authors.forename: Hyang-Min
authors.initials: HM
authors.lastname: Cheong
authors.affiliation: Institute for Diagnostic Markers, Eudipia Inc, Osong 28160, Korea.
authors.forename: Yoonsung
authors.initials: Y
authors.lastname: Kang
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Kangwon National University, Chuncheon 24341, Korea.
authors.forename: Keun-Cheol
authors.initials: KC
authors.lastname: Kim
mesh_terms: D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004795:Enzyme Stability / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D011496:Protein Methyltransferases / Q000378:metabolism*; D055550:Protein Stability / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D016760:Proto-Oncogene Proteins c-fos; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C454062:SETDB1 protein, human