Department of Biological Sciences, College of Natural Sciences, Kangwon National University, Chuncheon 24341, Korea.
Division of Respiratory Viruses, Center for Disease Control and Prevention, Korea National Institute of Health, Osong 28160, Korea.
BMB Rep. 2016 Apr;49(4):238-43. doi: 10.5483/bmbrep.2016.49.4.031.
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].
抗癌药物的疗效取决于多种信号通路，这些信号通路可以被正向或负向调节。在这项研究中，我们发现，由于 SETDB1 固有不稳定性，几种抗癌药物在转录水平下调 SETDB1 HMTase。通过 RNA 序列分析，我们确定 FosB 是在抗癌药物治疗过程中受到 SETDB1 调控的。阿霉素、紫杉醇和 siSETDB1 的处理增加了 FosB 的表达。此外，FosB 与增殖率的增加有关。与转染 siFosB 相比，共转染 siFosB 和 siSETDB1 的细胞增殖率略有增加。此外，FosB 受到多种激酶途径的调节。ChIP 分析表明，SETDB1 和 H3K9me3 与 FosB 启动子的特定区域相互作用。这些结果表明，SETDB1 介导的 FosB 表达是一种常见的分子现象，可能是抗癌药物治疗过程中细胞增殖增加的新途径。[BMB Reports 2016;49(4):238-243]。
