| First Author | Shen B | Year | 2020 |
| Journal | Biomed Res Int | Volume | 2020 |
| Pages | 9563851 | PubMed ID | 33083492 |
| Mgi Jnum | J:306841 | Mgi Id | MGI:6717937 |
| Doi | 10.1155/2020/9563851 | Citation | Shen B, et al. (2020) Lack of PPARbeta/delta-Inactivated SGK-1 Is Implicated in Liver Carcinogenesis. Biomed Res Int 2020:9563851 |
| abstractText | Objective: The present study examined the role of PPARbeta/delta in hepatocellular carcinoma (HCC). Methods: The effect of PPARbeta/delta on HCC development was analyzed using PPARbeta/delta-overexpressed liver cancer cells and PPARbeta/delta-knockout mouse models. Results: PPARbeta/delta ((-/-)) mice were susceptible to diethylnitrosamine- (DEN-) induced HCC (87.5% vs. 37.5%, p < 0.05). In addition, PPARbeta/delta-overexpressed HepG2 cells had reduced proliferation, migration, and invasion capabilities accompanied by increased apoptosis and cell cycle arrest at the G0/G1 phase. Moreover, differential gene expression profiling uncovered that the levels of serine/threonine-protein kinase (SGK-1) mRNA and its encoded protein were reduced in PPARbeta/delta-overexpressed HepG2 cells. Consistently, elevated SGK-1 levels were found in PPARbeta/delta ((-/-)) mouse livers as well as PPARbeta/delta-knockdown human SMMC-7721 HCC cells. Chromatin immunoprecipitation (ChIP) assays followed by real-time quantitative polymerase chain reaction (qPCR) assays further revealed the binding of PPARbeta/delta to the SGK-1 regulatory region in HepG2 cells. Conclusions: Due to the known tumor-promoting effect of SGK1, the present data suggest that PPARbeta/delta-deactivated SGK1 is a novel pathway for inhibiting liver carcinogenesis. |
