PIGU promotes hepatocellular carcinoma progression through activating NF-κB pathway and increasing immune escape

Abstract

Hepatocellular carcinoma (HCC) is the sixth most common malignancy and has the third highest mortality rate among all tumors. Previous studies found that phosphatidylinositol glycan anchor biosynthesis class U (PIGU) was highly expressed in hepatocellular carcinoma (HCC), while the function of PIGU in HCC remains unknown. Here, we deeply investigated this issue. The expression levels of PIGU in HCC cells were measured by Western blotting. The functions of PIGU in HCC cells were assessed in vitro, followed by assessing the nuclear factor-kappa B (NF-κB) pathway-related protein levels. The xenograft mouse models were conducted to investigate the effects of PIGU in vivo. Moreover, the effects of PIGU downregulation on natural killer (NK)-92 cell-mediated cell killing were detected. The results showed that PIGU was highly expressed in HCC cells compared with normal liver cells. Functional studies showed that PIGU promoted viability, cell cycle progression, migration, and invasion and suppressed apoptosis in HCC cells. Mechanism studies indicated that PIGU silencing blocked the NF-κB pathway and the blockade of the NF-κB pathway reversed the effects of PIGU overexpression on HCC cell function, including cell viability, migration, invasion, and apoptosis. In vivo studies further verified the effects of PIGU on HCC cell function, and demonstrated that PIGU knockdown suppressed tumorigenesis. Additionally, we proved that PIGU downregulation significantly enhanced the sensitivity of HCC cells to NK-92 cell cytolysis. Collectively, PIGU may promote HCC progression through activating the NF-κB pathway and promoting immune escape, indicating that PIGU may serve as a promising therapeutic target for HCC treatment.