核赖氨酸特异性去甲基化酶1（LSD1）在人肝癌细胞中的细胞质易位是由其抑制剂诱导的。
Cytoplasmic translocation of nuclear LSD1 () in human hepatoma cells is induced by its inhibitors.
作者信息
Yabuta Suemi, Shidoji Yoshihiro
机构信息
Molecular & Cellular Biology, Graduate School of Human Health Science, University of Nagasaki, 1-1-1 Academy Hills, Nagayo, Nagasaki 851-2195, Japan.
出版信息
Hepat Oncol. 2019 Jun 5;6(2):HEP13. doi: 10.2217/hep-2018-0008.
AIM
Histone-modifiable lysine-specific demethylase-1 (LSD1/KDM1A) is an oncoprotein upregulated in cancers, including hepatoma. We previously reported that the hepatoma-preventive geranylgeranoic acid (GGA) inhibits KDM1A at the same IC as that of the clinically used tranylcypromine. Here, we report that these inhibitors induce the cytoplasmic translocation of nuclear KDM1A in a human hepatoma-derived cell line.
METHODS & RESULTS: Immunofluorescence studies revealed that KDM1A was cytoplasmically localized in HuH-7 cells 3 h after GGA or tranylcypromine addition. However, GGA did not affect the subcellular localization of another histone lysine-specific demethylase, KDM5A. This suggests that GGA-induced translocation is KDM1A specific.
CONCLUSION
These data demonstrate, for the first time, that KDM1A inhibitors specifically induce the cytoplasmic translocation of nuclear KDM1A.
目的
组蛋白可修饰的赖氨酸特异性去甲基化酶-1（LSD1/KDM1A）是一种在包括肝癌在内的多种癌症中上调的癌蛋白。我们之前报道过，具有预防肝癌作用的香叶基香叶酸（GGA）与临床使用的反苯环丙胺一样，能在相同的半数抑制浓度（IC）下抑制KDM1A。在此，我们报道这些抑制剂在人肝癌衍生细胞系中诱导核KDM1A发生细胞质转位。
方法与结果
免疫荧光研究显示，在添加GGA或反苯环丙胺3小时后，KDM1A定位于HuH-7细胞的细胞质中。然而，GGA并不影响另一种组蛋白赖氨酸特异性去甲基化酶KDM5A的亚细胞定位。这表明GGA诱导的转位是KDM1A特异性的。
结论
这些数据首次证明，KDM1A抑制剂能特异性诱导核KDM1A的细胞质转位。
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