{"title":"KDM6A 通过激活 LAMP3 促进胰腺癌的血管生成、迁移和侵袭","authors":"Liang Xu, Sunfu Fan, Dafei Xie, Yongqi Yu","doi":"10.1615/critreveukaryotgeneexpr.2024054038","DOIUrl":null,"url":null,"abstract":"KDM6A is abnormally expressed in various cancer. This study aimed to investigate the potential of KDM6A in pancreatic cancer (PC). mRNA expression was calculated by RT-qPCR. Protein expression was detected by western blot. Cell viability was measured by CCK-8 assay. Cell angiogenesis was determined by tube formation assay. Cell migration and invasion were determined by transwell assay. We found that KDM6A was upregulated in PC patients and cells. Interestingly, KDM6A deficiency inhibited the proliferation and angiogenesis of PC cells. Moreover, KDM6A knockdown suppressed the migration and invasion of PC cells. Additionally, KDM6A upregulated the expression of LAMP3 via driving demethylation of H3K27me3. Overexpression of LAMP3 reversed the effects of KDM6A knockdown and contributed to the angiogenesis and aggressiveness of PC cells. In summary, KDM6A-mediated demethylation of H3K27me3 promotes the transcription of LAMP3, resulting the angiogenesis and aggressiveness of PC. Therefore, targeting KDM6A may be an anti-angiogenetic strategy for PC.","PeriodicalId":56317,"journal":{"name":"Critical Reviews in Eukaryotic Gene Expression","volume":"61 1","pages":""},"PeriodicalIF":1.5000,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"KDM6A promotes angiogenesis, migration, and invasion of pancreatic cancer via activating LAMP3\",\"authors\":\"Liang Xu, Sunfu Fan, Dafei Xie, Yongqi Yu\",\"doi\":\"10.1615/critreveukaryotgeneexpr.2024054038\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"KDM6A is abnormally expressed in various cancer. This study aimed to investigate the potential of KDM6A in pancreatic cancer (PC). mRNA expression was calculated by RT-qPCR. Protein expression was detected by western blot. Cell viability was measured by CCK-8 assay. Cell angiogenesis was determined by tube formation assay. Cell migration and invasion were determined by transwell assay. We found that KDM6A was upregulated in PC patients and cells. Interestingly, KDM6A deficiency inhibited the proliferation and angiogenesis of PC cells. Moreover, KDM6A knockdown suppressed the migration and invasion of PC cells. Additionally, KDM6A upregulated the expression of LAMP3 via driving demethylation of H3K27me3. Overexpression of LAMP3 reversed the effects of KDM6A knockdown and contributed to the angiogenesis and aggressiveness of PC cells. In summary, KDM6A-mediated demethylation of H3K27me3 promotes the transcription of LAMP3, resulting the angiogenesis and aggressiveness of PC. Therefore, targeting KDM6A may be an anti-angiogenetic strategy for PC.\",\"PeriodicalId\":56317,\"journal\":{\"name\":\"Critical Reviews in Eukaryotic Gene Expression\",\"volume\":\"61 1\",\"pages\":\"\"},\"PeriodicalIF\":1.5000,\"publicationDate\":\"2024-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Critical Reviews in Eukaryotic Gene Expression\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1615/critreveukaryotgeneexpr.2024054038\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Critical Reviews in Eukaryotic Gene Expression","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1615/critreveukaryotgeneexpr.2024054038","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
KDM6A 在多种癌症中异常表达。本研究旨在探讨 KDM6A 在胰腺癌（PC）中的潜在作用。蛋白表达用 Western 印迹法检测。细胞活力通过 CCK-8 试验测定。通过试管形成试验测定细胞血管生成。细胞迁移和侵袭通过透孔试验进行测定。我们发现 KDM6A 在 PC 患者和细胞中上调。有趣的是，KDM6A 缺乏会抑制 PC 细胞的增殖和血管生成。此外，KDM6A 基因敲除抑制了 PC 细胞的迁移和侵袭。此外，KDM6A通过驱动H3K27me3的去甲基化上调LAMP3的表达。LAMP3的过度表达逆转了KDM6A敲除的效果，并促进了PC细胞的血管生成和侵袭性。综上所述，KDM6A介导的H3K27me3去甲基化促进了LAMP3的转录，导致了PC的血管生成和侵袭性。因此，靶向 KDM6A 可能是 PC 的一种抗血管生成策略。
KDM6A promotes angiogenesis, migration, and invasion of pancreatic cancer via activating LAMP3
KDM6A is abnormally expressed in various cancer. This study aimed to investigate the potential of KDM6A in pancreatic cancer (PC). mRNA expression was calculated by RT-qPCR. Protein expression was detected by western blot. Cell viability was measured by CCK-8 assay. Cell angiogenesis was determined by tube formation assay. Cell migration and invasion were determined by transwell assay. We found that KDM6A was upregulated in PC patients and cells. Interestingly, KDM6A deficiency inhibited the proliferation and angiogenesis of PC cells. Moreover, KDM6A knockdown suppressed the migration and invasion of PC cells. Additionally, KDM6A upregulated the expression of LAMP3 via driving demethylation of H3K27me3. Overexpression of LAMP3 reversed the effects of KDM6A knockdown and contributed to the angiogenesis and aggressiveness of PC cells. In summary, KDM6A-mediated demethylation of H3K27me3 promotes the transcription of LAMP3, resulting the angiogenesis and aggressiveness of PC. Therefore, targeting KDM6A may be an anti-angiogenetic strategy for PC.
期刊介绍：
Critical ReviewsTM in Eukaryotic Gene Expression presents timely concepts and experimental approaches that are contributing to rapid advances in our mechanistic understanding of gene regulation, organization, and structure within the contexts of biological control and the diagnosis/treatment of disease. The journal provides in-depth critical reviews, on well-defined topics of immediate interest, written by recognized specialists in the field. Extensive literature citations provide a comprehensive information resource.
Reviews are developed from an historical perspective and suggest directions that can be anticipated. Strengths as well as limitations of methodologies and experimental strategies are considered.
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