| First Author | Wang S | Year | 2022 |
| Journal | Cancer Gene Ther | Volume | 29 |
| Issue | 2 | Pages | 202-214 |
| PubMed ID | 33558702 | Mgi Jnum | J:333835 |
| Mgi Id | MGI:7442344 | Doi | 10.1038/s41417-021-00300-0 |
| Citation | Wang S, et al. (2022) Knockout of ASPP2 promotes DEN-induced hepatocarcinogenesis via the NF-kappaB pathway in mice. Cancer Gene Ther 29(2):202-214 |
| abstractText | 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-kappaB signaling pathway. Further, ChIP-Seq results revealed that NF-kappaB target genes were dramatically increased in APKO mice. In contrast, blockade of the NF-kappaB 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-kappaB pathway to promote the occurrence of DEN-induced hepatocarcinogenesis, indicating that ASPP2 may be a potential target for the treatment of hepatocarcinoma. |
