Translational research focusing on the regulation of proteasome by Gankyrin

点击翻译按钮获取中文摘要

Liver-specific p38-alpha ablation was found to enhance ROS accumulation, because it reduced the expression ofHSP25. p38-alpha-deficiency also increased the expression of SOX2, c-Jun and Gankyrin and led to enhanced TAA-induced hepatocarcinogenesis. The up-regulation of SOX2 and c-Jun was prevented by administration of the antioxidant butylated hydroxyanisole. The risk of human HCC recurrence is positively correlated with ROS accumulation in the liver. Augmented oxidative stress of liver parenchymal cells may explain the close relationship between liver fibrosis and hepatocarcinogenesis. In addition, expression of CD133, a cancer stem cell marker, was significantly correlated with Gankyrin expression. Gankyrin knockdown decreased the expression of vascular endothelial growth factor (VEGF) and stemness factors such as Nanog and Oct-4 in colorectal and liver cancer cells.