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首页> 外文期刊>Journal of experimental & clinical cancer research : >HBP1-mediated transcriptional repression of AFP inhibits hepatoma progression
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HBP1-mediated transcriptional repression of AFP inhibits hepatoma progression

机译：HBP1介导的AFP转录抑制抑制肝癌进展

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Hepatoma is a common malignancy of the liver. The abnormal high expression of alpha-fetoprotein (AFP) is intimately associated with hepatoma progress, but the mechanism of transcriptional regulation and singularly activation of AFP gene in hepatoma is not clear. The expression of transcription factor HBP1 and AFP and clinical significance were further analyzed in hepatoma tissues from the patients who received surgery or TACE and then monitored for relapse for up 10?years. HBP1-mediated transcriptional regulation of AFP was analyzed by Western blotting, Luciferase assay, Realtime-PCR, ChIP and EMSA. After verified the axis of HBP-AFP, its impact on hepatoma was measured by MTT, Transwell and FACS in hepatoma cells and by tumorigenesis in HBP1?/? mice. The relative expressions of HBP1 and AFP correlated with survival and prognosis in hepatoma patients. HBP1 repressed the expression of AFP gene by directly binding to the AFP gene promoter. Hepatitis B Virus (HBV)-encoded protein HBx promoted malignancy in hepatoma cells through binding to HBP1 directly. Icaritin, an active ingredient of Chinese herb epimedium, inhibited malignancy in hepatoma cells through enhancing HBP1 transrepression of AFP. The repression of AFP by HBP1 attenuated AFP effect on PTEN, MMP9 and caspase-3, thus inhibited proliferation and migration, and induced apoptosis in hepatoma cells. The deregulation of AFP by HBP1 contributed to hepatoma progression in mice. Our data clarify the mechanism of HBP1 in inhibiting the expression of AFP and its suppression in malignancy of hepatoma cells, providing a more comprehensive theoretical basis and potential solutions for the diagnosis and treatment of hepatoma.
机译：肝癌是肝脏的常见恶性肿瘤。 α-胎蛋白（AFP）的异常高表达与肝癌进展密切相关，但转录调控机制和肝癌中AFP基因的奇异活化的机制尚不清楚。来自接受手术或TACE的患者的肝癌组织中进一步分析了转录因子HBP1和AFP的表达以及临床意义，然后监测复发10？年。通过Western印迹，荧光素酶测定，RealTime-PCR，芯片和EMSA分析HBP1介导的AFP转录调节。经过验证HBP-AFP的轴后，其对肝癌细胞中的MTT，Transwell和Facs测量其对肝癌的影响，并在HBP1中的肿瘤内酯测量？/？老鼠。 HBP1和AFP的相对表达与肝癌患者的存活和预后相关。 HBP1通过直接与AFP基因启动子结合来压抑AFP基因的表达。乙型肝炎病毒（HBV） - 蛋白质HBX通过直接与HBP1结合促进肝癌细胞中的恶性肿瘤。 Icaritin是中国草药淫羊藿的活性成分，通过增强AFP的HBP1转血细胞抑制肝癌细胞中的恶性肿瘤。通过HBP1抑制AFP对PTEN，MMP9和Caspase-3的AFP效应，从而抑制增殖和迁移，并在肝癌细胞中诱导细胞凋亡。 HBP1对AFP的放松管制有助于小鼠的肝癌进展。我们的数据阐明了HBP1抑制AFP表达的机制及其在恶性肝癌细胞恶性肿瘤中的抑制，为肝癌的诊断和治疗提供了更全面的理论基础和潜在的解决方案。

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