Role of RbBP5 and H3K4me3 in the vicinity of Snail transcription start site during epithelial-mesenchymal transition in prostate cancer cell.
Role of RbBP5 and H3K4me3 in the vicinity of Snail transcription start site during epithelial-mesenchymal transition in prostate cancer cell.
复制标题
RbBP5和H3K4me3在前列腺癌细胞上皮间质转化过程中Snail转录起始位点附近的作用
DOI：
10.18632/oncotarget.11549
复制
发表时间：
2016-10-04
期刊：
影响因子：
--
通讯作者：
Yu XG
中科院分区：
文献类型：
--
作者：
Li D;Sun H;Sun WJ;Bao HB;Si SH;Fan JL;Lin P;Cui RJ;Pan YJ;Wen SM;Zheng XL;Yu XG
EMT（上皮-间质转化）发生在广泛的肿瘤类型中，并且已被证明对转移至关重要。组蛋白的表观遗传修饰有助于染色质结构并导致基因表达的改变。组蛋白H3赖氨酸4（H3 K4 me 3）的三甲基化与活跃转录基因的启动子相关，并且可以充当转录开/关开关。RbBP 5是COMPASS/ -样复合物的组分，其催化H3 K4 me 3形成。在本研究中，我们发现在TGF-β 1诱导前列腺癌细胞系DU 145 EMT的过程中，H3 K4 me 3富集和RbBP 5结合在Snail（SNAI 1）转录起始位点附近增加。敲低RbBP 5显著降低Snail表达和EMT。EMT期间RbBP 5在Snail TSS的募集和H3 K4 me 3的形成取决于SMAD 2/3和CBP在Snail TSS的结合。这项研究通过组蛋白修饰H3 K4 me 3将SMAD 2/3信号与Snail转录联系起来。此外，我们的研究还表明RbBP 5甚至WRAD可能是治疗前列腺癌转移的有希望的治疗候选者，并且DU 145细胞以自分泌/旁分泌方式维持其不完整的间充质状态。
EMT (epithelial-mesenchymal transition) occurs in a wide range of tumor types, and has been shown to be crucial for metastasis. Epigenetic modifications of histones contribute to chromatin structure and result in the alterations in gene expression. Tri-methylation of histone H3 lysine 4 (H3K4me3) is associated with the promoters of actively transcribed genes and can serve as a transcriptional on/off switch. RbBP5 is a component of the COMPASS/ -like complex, which catalyzes H3K4me3 formation. In this study, we found that in the process of TGF-Beta1 induced EMT in the prostate cancer cell line DU145, H3K4me3 enrichment and RbBP5 binding increased in the vicinity of Snail (SNAI1) transcription start site. Knocking-down of RbBP5 notably decreased Snail expression and EMT. Recruitment of RbBP5 and formation of H3K4me3 at Snail TSS during EMT depend on binding of SMAD2/3 and CBP at Snail TSS. This study links the SMAD2/3 signal with Snail transcription via a histone modification - H3K4me3. Furthermore, our research also demonstrates that RbBP5 and even WRAD may be a promising therapeutic candidates in treating prostate cancer metastasis, and that DU145 cells maintain their incomplete mesenchymal state in an auto/paracrine manner.