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http://dx.doi.org/10.5483/BMBRep.2016.49.4.031

SETDB1 mediated FosB expression increases the cell proliferation rate during anticancer drug therapy  

Na, Han-Heom (Department of Biological Sciences, College of Natural Sciences, Kangwon National University)
Noh, Hee-Jung (Department of Biological Sciences, College of Natural Sciences, Kangwon National University)
Cheong, Hyang-Min (Division of Respiratory Viruses, Center for Disease Control and Prevention, Korea National Institute of Health)
Kang, Yoonsung (Institute for Diagnostic Markers, Eudipia Inc)
Kim, Keun-Cheol (Department of Biological Sciences, College of Natural Sciences, Kangwon National University)
Publication Information
BMB Reports / v.49, no.4, 2016 , pp. 238-243 More about this Journal
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.
Keywords
Anticancer drugs; Doxorubicin; Drug resistance; FosB; SETDB1;
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