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当代肿瘤药物靶点

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Research Article

C /EBPα通过与肝细胞癌中的PPARγ相互作用调节FOXC1调节肿瘤的生长

卷 20, 期 1, 2020

页: [59 - 66] 页: 8

弟呕挨: 10.2174/1568009619666190912161003

价格: $65

摘要

背景：叉头盒C1（FOXC1）是肿瘤中与癌症相关的重要基因。 PPAR-γ和C /EBPα都是参与肿瘤发展的转录调节因子。目的：旨在阐明肝癌中PPAR-γ，C /EBPα的功能以及肝癌中PPAR-γ，C /EBPα和FOXC1的关系。 方法：采用蛋白质印迹，免疫荧光染色和免疫组化方法评估蛋白质表达。使用qRT-PCR评估mRNA表达。进行Co-IP检测蛋白相互作用。并用ChIP和荧光报告基因检测来确定蛋白质与FOXC1启动子之间的结合。 结果：C /EBPα可与FOXC1启动子结合，PPAR-γ可增强C /EBPα的功能。人肝癌组织中C /EBPα和PPAR-γ的表达均与FOXC1负相关。共聚焦显示，C /EBPα与FOXC1在HepG2细胞中位于同一位置。 C /EBPα可以通过ChIP与FOXC1启动子结合。萤光素酶活性检测结果表明，C /EBPα可以抑制FOXC1启动子的活性，尤其是FOXC1启动子从-600到-300为关键结合位点。只有PPAR-γ不能影响荧光素酶活性，但可以增强C /EBPα的抑制作用。此外，Co-IP显示PPAR-γ可以与C /EBPα结合。当C /EBPα和PPAR-γ都高表达时，细胞增殖，迁移，侵袭和集落信息被极大地抑制。结合或不结合PPAR-γ激动剂MDG548处理的C /EBPα质粒在小鼠中均表现出较强的肿瘤抑制和FOXC1抑制作用。 结论：我们的数据确定靶向FOXC1的C /EBPα是肝癌的潜在决定因素，这为治疗HCC提供了新途径。但是，PPAR-γ对FOXC1表达没有影响。

关键词: HCC，FOXC1，PPAR-γ，C /EBPα，增殖，肝细胞癌。

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