Cytoplasmic translocation of nuclear LSD1 (KDM1A) in human hepatoma cells is induced by its inhibitors.

IF 1.2 Q4 ONCOLOGY Hepatic Oncology Pub Date : 2019-06-05 DOI:10.2217/hep-2018-0008

Suemi Yabuta, Yoshihiro Shidoji

引用次数: 7

Abstract

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 IC₅₀ 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.

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核LSD1 (KDM1A)在人肝癌细胞中的细胞质易位是由其抑制剂诱导的。

目的:组蛋白修饰赖氨酸特异性去甲基酶-1 (LSD1/KDM1A)是一种在包括肝癌在内的癌症中上调的癌蛋白。我们之前报道过，预防肝癌的香叶酸(GGA)抑制KDM1A的IC50与临床使用的丙基环丙氨酸相同。在这里，我们报道了这些抑制剂在人肝癌来源的细胞系中诱导核KDM1A的细胞质易位。方法与结果:免疫荧光研究显示，添加GGA或丙基环丙氨酸3小时后，KDM1A在HuH-7细胞中胞质定位。然而，GGA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诱导的易位是KDM1A特异性的。结论:这些数据首次证明了KDM1A抑制剂特异性诱导核KDM1A的细胞质易位。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Hepatic Oncology ONCOLOGY-

CiteScore

0.40

自引率

0.00%

发文量

审稿时长

13 weeks

期刊介绍： Primary liver cancer is the sixth most common cancer in the world, and the third most common cause of death from malignant disease. Traditionally more common in developing countries, hepatocellular carcinoma is becoming increasingly prevalent in the Western world, primarily due to an increase in hepatitis C virus infection. Emerging risk factors, such as non-alcoholic fatty liver disease and obesity are also of concern for the future. In addition, metastatic tumors of the liver are more common than primary disease. Some studies report hepatic metastases in as many as 40 to 50% of adult patients with extrahepatic primary tumors. Hepatic Oncology publishes original research studies and reviews addressing preventive, diagnostic and therapeutic approaches to all types of cancer of the liver, in both the adult and pediatric populations. The journal also highlights significant advances in basic and translational research, and places them in context for future therapy. Hepatic Oncology provides a forum to report and debate all aspects of cancer of the liver and bile ducts. The journal publishes original research studies, full reviews and commentaries, with all articles subject to independent review by a minimum of three independent experts. Unsolicited article proposals are welcomed and authors are required to comply fully with the journal''s Disclosure & Conflict of Interest Policy as well as major publishing guidelines, including ICMJE and GPP3.