{"title":"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。","authors":"Suemi Yabuta, Yoshihiro Shidoji","doi":"10.2217/hep-2018-0008","DOIUrl":null,"url":null,"abstract":"<p><strong>Aim: </strong>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<sub>50</sub> 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.</p><p><strong>Methods & results: </strong>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.</p><p><strong>Conclusion: </strong>These data demonstrate, for the first time, that KDM1A inhibitors specifically induce the cytoplasmic translocation of nuclear KDM1A.</p>","PeriodicalId":44854,"journal":{"name":"Hepatic Oncology","volume":"6 2","pages":"HEP13"},"PeriodicalIF":1.2000,"publicationDate":"2019-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/hep-2018-0008","citationCount":"7","resultStr":"{\"title\":\"Cytoplasmic translocation of nuclear LSD1 (<i>KDM1A</i>) in human hepatoma cells is induced by its inhibitors.\",\"authors\":\"Suemi Yabuta, Yoshihiro Shidoji\",\"doi\":\"10.2217/hep-2018-0008\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Aim: </strong>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<sub>50</sub> 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.</p><p><strong>Methods & results: </strong>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.</p><p><strong>Conclusion: </strong>These data demonstrate, for the first time, that KDM1A inhibitors specifically induce the cytoplasmic translocation of nuclear KDM1A.</p>\",\"PeriodicalId\":44854,\"journal\":{\"name\":\"Hepatic Oncology\",\"volume\":\"6 2\",\"pages\":\"HEP13\"},\"PeriodicalIF\":1.2000,\"publicationDate\":\"2019-06-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.2217/hep-2018-0008\",\"citationCount\":\"7\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Hepatic Oncology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.2217/hep-2018-0008\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hepatic Oncology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2217/hep-2018-0008","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"ONCOLOGY","Score":null,"Total":0}
Cytoplasmic translocation of nuclear LSD1 (KDM1A) in human hepatoma cells is induced by its inhibitors.
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.
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.
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