| First Author | Kim H | Year | 2021 |
| Journal | Biochem Biophys Res Commun | Volume | 563 |
| Pages | 98-104 | PubMed ID | 34062393 |
| Mgi Jnum | J:344819 | Mgi Id | MGI:7579523 |
| Doi | 10.1016/j.bbrc.2021.05.051 | Citation | Kim H, et al. (2021) ZNF746/PARIS promotes the occurrence of hepatocellular carcinoma. Biochem Biophys Res Commun 563:98-104 |
| abstractText | Hepatocellular carcinoma (HCC) is the most common primary liver cancer to cause liver cancer related deaths worldwide. Zinc finger protein 746 (ZNF746), initially identified as a Parkin-interacting substrate (PARIS), acts as a transcriptional repressor of peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) in Parkinson's disease. As recent studies reported that PARIS is associated with cancer onset, we investigated whether PARIS is associated with HCC. We found an increase in insoluble parkin and PARIS accumulation in the liver of diethylnitrosamine (DEN)-injected mice, leading to the downregulation of PGC-1alpha and nuclear respiratory factor 1 (NRF1). Interestingly, the occurrence of DEN-induced tumors was significantly alleviated in the livers of DEN-injected PARIS knockout mice compared to DEN-injected wild-type mice, suggesting that PARIS is involved in DEN-induced hepatocellular tumorigenesis. Moreover, H(2)O(2)-treated Chang liver cells showed accumulation of PARIS and downregulation of PGC-1alpha and NRF1. Thus, these results suggest that PARIS upregulation by oncogenic stresses can promote cancer progression by suppressing the transcriptional level of PGC-1alpha, and the modulation of PARIS can be a promising therapeutic target for HCC. |
