Shokraii Fatemeh, Moharrami Maryam, Motamed Nasrin, Shahhoseini Maryam, Totonchi Mehdi, Ezzatizadeh Vahid, Firouzi Javad, Khosravani Pardis, Ebrahimi Marzieh
Department of Developmental Biology, University of Science and Culture, ACECR, Tehran, Iran.
Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
Cell J. 2019 Jul;21(2):124-134. doi: 10.22074/cellj.2019.5702. Epub 2019 Feb 20.
Cadherin-1 () plays an important role in the metastasis, while expression of this protein is under control of epigenetic changes on its gene promoter. Therefore we evaluated both DNA methylation (DNAmet) and histone modification marks of in prostate cancer stem like cells (PCSLCs).
In this experimental study, we isolated PCSLCs using cell surface marker and prostaspheroid formation, respectively. The cells isolated from both methods were characterized and then the levels of H3K4me2, H3K27me3, H3K9me2/3 and H3K9ac as well as DNAmet were assessed in promoter of the isolated cells.
The CD44 CD49 cells were not validated as PCSLCs. However, prostaspheres overexpressed stemness related genes and had higher ability of invasion potential, associated with reduction in expression. Epigenetic status analysis showed that promoter was hypo-methylated. Histone modifications of H3K9ac and H3K4me3 were significantly reduced, in parallel with an increased level of H3K27me3.
Our results suggest that slight decrease of DNAmet of the CpG island in promoter does not significantly contribute to the change of expression. Therefore, histone modifications are responsible in repressing in PCSLCs.
钙黏蛋白-1( )在转移过程中起重要作用,而该蛋白的表达受其基因启动子表观遗传变化的调控。因此,我们评估了前列腺癌干细胞样细胞(PCSLCs)中 的DNA甲基化(DNAmet)和组蛋白修饰标记。
在本实验研究中,我们分别使用细胞表面标志物和前列腺球形成来分离PCSLCs。对两种方法分离得到的细胞进行表征,然后评估分离细胞 启动子中H3K4me2、H3K27me3、H3K9me2/3和H3K9ac以及DNAmet的水平。
CD44 CD49细胞未被确认为PCSLCs。然而,前列腺球过度表达干性相关基因,具有更高的侵袭潜能,且与 表达降低相关。表观遗传状态分析表明 启动子低甲基化。H3K9ac和H3K4me3的组蛋白修饰显著减少,同时H3K27me3水平升高。
我们的结果表明, 启动子中CpG岛的DNAmet轻微降低对 表达的变化没有显著贡献。因此,组蛋白修饰负责在PCSLCs中抑制 。