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

Abstract

ObjectiveThe aim of this study is to elucidate the role of PRDX1 in hepatocellular carcinoma using hepatomacells.Materials and MethodsIn this experimental study, we elucidated role of PRDX1, using hepatoma cell lines.ResultsPRDX1 was upregulated in different types of cancers, including lung adenocarcinoma, breast cancer and livercancer reported by several studies. nevertheless, mechanism of inducing liver cell death by PRDX1 remains largelyunknown. 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 ofPRDX1. We observed that overexpression of PRDX1 significantly enhanced proliferation of hepatoma cell lines, whileknock-down of this gene showed significant inhibitory effects. We found that knock-down of PRDX1 activated cleavedcaspase-3, caspase-9 proteins and Poly [ADP-ribose] polymerase 1 (PARP-1), which further executed apoptoticprocess, 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 apoptoticproteins, suggesting a significant role of PRDX1 knock-down in apoptosis. Finally, we showed that knock-down ofPRDX1 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 animportant role of PRDX1 in regulating proliferation of hepatoma cells and thus future studies are required to validate itseffect on hepatcoytes.ConclusionWe propose that future works on PRDX1 inhibitors may act as a therapeutic candidate for treatment of liver cancer.

Keywords

• hepatocellular carcinoma
• liver cancer
• peroxiredoxins
• prdx1