文章：

敲除ASPP2可通过NF-κB途径促进小鼠DEN-诱导的肝癌发生

Knockout of ASPP2 promotes DEN-induced hepatocarcinogenesis via the NF-κB pathway in mice 

原文发布日期：2021-02-08 

英文摘要：

Apoptosis-stimulating protein p53 2 (ASPP2) is a member of the p53-binding protein family, which is closely related to tumor development. However, the precise mechanism of ASPP2 in liver inflammation and tumorigenesis remains largely unclear. We aimed to characterize the mechanistic significance and clinical implication of ASPP2 in hepatitis and hepatocellular carcinoma (HCC). In this study, ASPP2 knockout (APKO) mice were generated to confirm the role of ASPP2 in the development of hepatitis and HCC. Liver tissues from mice were analyzed by immunohistochemistry, Western blotting, proteomic analysis, ChIP-Seq, and qRT-PCR to evaluate the role of ASPP2 in DEN-induced hepatitis and HCC. We found that APKO promoted the formation of hepatitis/hepatocarcinoma and the increased expression of proinflammatory factors. The proteomics and Western blotting results showed that APKO activated the NF-κB signaling pathway. Further, ChIP-Seq results revealed that NF-κB target genes were dramatically increased in APKO mice. In contrast, blockade of the NF-κB pathway by QNZ reduced the expression of proinflammatory factors and the susceptibility of APKO mice to DEN-induced hepatocarcinogenesis. These results suggested that the absence of ASPP2 activates the NF-κB pathway to promote the occurrence of DEN-induced hepatocarcinogenesis, indicating that ASPP2 may be a potential target for the treatment of hepatocarcinoma. 

摘要翻译： 

凋亡刺激蛋白p53 2（ASPP2）是p53结合蛋白家族成员，与肿瘤发展密切相关。然而，ASPP2在肝脏炎症和肿瘤发生中的具体机制尚不明确。本研究旨在阐明ASPP2在肝炎和肝细胞癌（HCC）中的机制意义及临床价值。我们构建了ASPP2基因敲除（APKO）小鼠以验证其在肝炎和HCC发展中的作用，通过免疫组化、Western blotting、蛋白质组学分析、ChIP-Seq和qRT-PCR技术对小鼠肝组织进行分析，评估ASPP2在DEN诱导肝炎和HCC中的作用。研究发现APKO促进肝炎/肝癌形成并增强促炎因子表达。蛋白质组学和Western blotting结果表明APKO激活了NF-κB信号通路。ChIP-Seq结果进一步显示APKO小鼠中NF-κB靶基因显著增加。相反，使用QNZ阻断NF-κB通路可降低促炎因子表达，并减少APKO小鼠对DEN诱导肝癌发生的易感性。这些结果表明ASPP2缺失通过激活NF-κB通路促进DEN诱导的肝癌发生，提示ASPP2可能成为肝癌治疗的潜在靶点。

原文链接：

Knockout of ASPP2 promotes DEN-induced hepatocarcinogenesis via the NF-κB pathway in mice