PRDX1 Influences The Occurrence and Progression of Liver Cancer by Inhibiting Mitochondrial Apoptosis Pathway

Objective: The aim of this study is to elucidate the role of PRDX1 in hepatocellular carcinoma using hepatoma cells. Materials and Methods: In this experimental study, we elucidated role of PRDX1, using hepatoma cell lines. Results: PRDX1 was upregulated in different types of cancers, including lung adenocarcinoma, breast cancer and liver cancer reported by several studies. nevertheless, mechanism of inducing liver cell death by PRDX1 remains largely unknown. Here, we showed that PRDX1 expression is enhanced in different cell lines. Here, we used western blot, quantitative real time polymerase chain reaction (qRT-PCR) and different biochemical assays to explore the role of PRDX1. We observed that overexpression of PRDX1 significantly enhanced proliferation of hepatoma cell lines, while knock-down of this gene showed significant inhibitory effects. We found that knock-down of PRDX1 activated cleaved caspase-3, caspase-9 proteins and Poly [ADP-ribose] polymerase 1 (PARP-1), which further executed apoptotic process, leading to cell death. We found that PRDX1 knock-down significantly produced mitochondrial fragmentation. We showed that silencing PRDX1 led to the loss of B-cell lymphoma 2 (Bcl-2) and activated Bcl-2-like protein 11 (Bim) which further induced Bax activation. Bax further released cytochrome c from mitochondria and induced apoptotic proteins, suggesting a significant role of PRDX1 knock-down in apoptosis. Finally, we showed that knock-down of PRDX1 significantly activated expression of Dynein-related protein 1 (Drp1), fission 1 (Fis1) and dynamin-2 (Dyn2) suggesting a crucial role of PRDX1 in mitochondrial fragmentation and apoptosis conditions. This study highlighted an important role of PRDX1 in regulating proliferation of hepatoma cells and thus future studies are required to validate its effect on hepatcoytes. Conclusion: We propose that future works on PRDX1 inhibitors may act as a therapeutic candidate for treatment of liver cancer.