PLU1 histone demethylase decreases the expression of KAT5 and enhances the invasive activity of the cells
PLU1 histone demethylase decreases the expression of KAT5 and enhances the invasive activity of the cells
复制标题
PLU1组蛋白去甲基化酶降低KAT5的表达并增强细胞的侵袭活性
DOI：
10.1042/bj20110343
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Suzuki T
中科院分区：
文献类型：
--
作者：
Yoshida M;Ishimura A;Terashima M;Enkhbaatar Z;Nozaki N;Satou K;Suzuki T
PLU1是编码H3K4(组蛋白H3的Lys4)去甲基酶的候选癌基因。在本研究中，我们发现PLU1的异位表达增强了依赖于其去甲基酶活性的弱侵袭性细胞的侵袭能力。PLU1通过其启动子上的H3K4去甲基化抑制KAT5基因的表达。提示PLU1对KAT5的调控可能与PLU1诱导的细胞侵袭有关。首先，KAT5基因的敲除同样增加了细胞的侵袭潜力。其次，PLU1在高侵袭性癌细胞中被敲除后，KAT5的表达增加，侵袭活性降低。第三，同时敲除KAT5可部分缓解PLU1基因敲除对细胞侵袭的抑制作用。最后，我们发现受KAT5转录调控的CD82可能是PLU1促进细胞侵袭的候选效应因子。本研究证实了PLU1过度表达和伴随的表观遗传失调在癌症进展中的功能贡献。
PLU1 is a candidate oncogene that encodes H3K4 (Lys4of histone H3) demethylase. In the present study, we found that ectopic expression of PLU1 enhanced the invasive potential of the weakly invasive cells dependent on its demethylase activity. PLU1 was shown to repress the expression of the KAT5 gene through its H3K4 demethylation on the promoter. The regulation of KAT5 by PLU1 was suggested to be responsible for PLU1-induced cell invasion. First, knockdown of KAT5 similarly increased the invasive potential of the cells. Secondly, knockdown of PLU1 in the highly invasive cancer cells increased KAT5 expression and reduced the invasive activity. Thirdly, simultaneous knockdown of KAT5 partially relieved the suppression of cell invasion imposed by PLU1 knockdown. Finally, we found that CD82, which was transcriptionally regulated by KAT5, might be a candidate effector of cell invasion promoted by PLU1. The present study demonstrated a functional contribution of PLU1 overexpression with concomitant epigenetic dysregulation in cancer progression.