Abstract
Retinoids are known to be involved in suppression of several kinds of cancers, including hepatocellular carcinoma (HCC). To test the hypothesis that shortage of vitamin A in hepatic stellate cells causes HCC during the course of chronic liver disease, we reported the transgenic mice, in which retinoic acid (RA) signaling is suppressed in a hepatocyte-specific manner, developed liver cancer at a high rate. Retinoids play an important role in liver pathophysiology including iron metabolism, insulin resistance, fatty acid oxidation and regulation of oxidative stress. These data suggest that exploring the metabolism of retinoids in liver diseases and their target genes provides us with useful information to understand the liver functions and diseases. The metabolism of retinoids was altered in liver diseases, including non-alcoholic fatty liver disease. We identified 26 genes using in silico analysis based on the gene information of a DR5 in the 5-Kb upstream of 36,341 EST clusteres. Of these genes, expression of OTUD7B, an upregulated by ATRA, serves as an indicator of cancer-specific survival in HCC patients. These efforts will hopefully improve the prognosis of the patients with liver diseases in the near future.
