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首页> 外文期刊>Anticancer Research: International Journal of Cancer Research and Treatment >Metastasis Suppressor NME1 Directly Activates Transcription of the ALDOC Gene in Melanoma Cells
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Metastasis Suppressor NME1 Directly Activates Transcription of the ALDOC Gene in Melanoma Cells

机译：转移抑制器NME1直接激活黑色素瘤细胞中的Aldoc基因的转录

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摘要

Background/Aim: NME/NM23 nucleoside diphosphate kinase 1 (NME1) is a metastasis suppressor gene, exhibiting reduced expression in metastatic cancers and the ability to suppress metastatic activity of cancer cells. We previously identified NME1-regulated genes with prognostic value in human melanoma. This study was conducted in melanoma cell lines aiming to elucidate the mechanism through which NME regulates one of these genes, aldolase C (ALDOC). Materials and Methods: ALDOC mRNA and protein expression was measured using qRT-PCR and immunoblot analyses. Promoter-luciferase constructs and chromatin immunoprecipitation were employed to measure the impact of NME1 on ALDOC transcription. Results: NME1 enhanced ALDOC transcription, evidenced by increased expression of ALDOC pre-mRNA and activity of an ALDOC promoter-luciferase module. NME1 was detected at the ALDOC promoter, and forced NME1 expression resulted in enhanced occupancy of the promoter by NME1, increased presence of epigenetic activation markers (H3K4me3 and H3K27ac), and recruitment of RNA polymerase II. Conclusion: This is the first study to indicate that NME1 induces transcription through its direct binding to the promoter region of a target gene.
机译：背景/目的：NME / NM23核苷二磷酸三磷酸激酶1（NME1）是转移抑制基因，表现出降低的转移性癌症表达和抑制癌细胞的转移活性的能力。我们以前鉴定了人黑素瘤中具有预后价值的NME1调节基因。该研究是在黑色素瘤细胞系中进行的，旨在阐明NME调节这些基因之一，醛糖酶C（Aldoc）的机制。材料和方法：使用QRT-PCR和免疫印迹分析测量Aldoc mRNA和蛋白质表达。使用启动子 - 荧光素酶构建体和染色质免疫沉淀法测量NME1对醛族转录的影响。结果：NME1增强的Aldoc转录，通过增加Aldoc促进剂 - 荧光素酶模块的Aldoc前mRNA和活性表达的增加。在Aldoc启动子处检测到NME1，强制NME1表达导致NME1增强了启动子的占用率，增加了表观遗传活化标志物（H3K4ME3和H3K27AC）的存在，以及RNA聚合酶II的募集。结论：这是第一项研究表明NME1通过其直接结合靶基因的启动子区诱导转录。

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