Knockout of ASPP2 promotes DEN-induced hepatocarcinogenesis via the NF-κB pathway in mice
| Autor: | Buxin Kou, Ling Yin, Mengyin Chai, Dexi Chen, Shanshan Wang, Yuxue Gao, Xue-Jun Lin, Xiaoni Liu |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Proteomics Cancer Research Carcinoma Hepatocellular Carcinogenesis Inflammation Biology medicine.disease_cause Proinflammatory cytokine 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine medicine Animals Humans Molecular Biology Hepatitis Mice Knockout Tumor Suppressor Proteins Liver Neoplasms NF-kappa B NF-κB medicine.disease digestive system diseases Blot 030104 developmental biology chemistry 030220 oncology & carcinogenesis Hepatocellular carcinoma Cancer research Molecular Medicine medicine.symptom Signal transduction |
| Zdroj: | Cancer gene therapy. 29(2) |
| ISSN: | 1476-5500 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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