RNF126 is a peroxisomal fate switch enabling redifferentiation therapy in hepatocellular carcinoma - PubMed
3 hours ago
- #redifferentiation therapy
- #hepatocellular carcinoma
- #pexophagy
- RNF126 is an E3 ubiquitin ligase that acts as a peroxisomal fate switch in hepatocellular carcinoma (HCC).
- Under hypoxia, HIF-2α induces RNF126 expression, which ubiquitinates peroxisomal transporter ABCD3, leading to pexophagy and peroxisome depletion.
- Peroxisome loss disrupts fatty acid oxidation and detoxification, contributing to hepatocyte dedifferentiation in HCC.
- Genetic ablation of RNF126 restores peroxisomal functions and inhibits hypoxic HCC growth.
- A small-molecule inhibitor (D665-1412) blocks RNF126-mediated pexophagy, stabilizes peroxisomes, and promotes redifferentiation of HCC cells.
- The HIF-2α-RNF126-ABCD3 axis drives HCC dedifferentiation, and targeting it offers a redifferentiation therapy approach for liver cancer.