Silencing PRDX3 Inhibits Growth and Promotes Invasion and Extracellular Matrix Degradation in Hepatocellular Carcinoma Cells

Abstract

PRDX3 is a mitochondrial peroxide reductase that regulates cellular redox state. It has been reported that PRDX3 is overexpressed in liver cancer, but how PRDX3 is involved in hepatocellular carcinoma (HCC) tumorigenesis and progression has not been well-characterized. In the present study, we established two stable cell lines by overexpressing or knocking down PRDX3 in HepG2 cells. We found that PRDX3 silencing decreased the growth rate of HepG2 cells and increased mtDNA oxidation. Quantitative proteomics identified 475 differentially expressed proteins between the PRDX3 knockdown and the control cells. These proteins were involved in antioxidant activity, angiogenesis, cell adhesion, cell growth, ATP synthesis, nucleic acid binding, redox, and chaperones. PRDX3 knockdown led to the down-regulation of ATP synthases and the decreased cellular ATP level, contributing to the slow-down of cell growth. Furthermore, silencing PRDX3 enhanced invasive properties of HepG2 cells via TIMP-1 down-regulation and the increased ECM degradation. Taken together, our results indicate that PRDX3 promotes HCC growth and mediates cell migration and invasiveness and is a potential therapeutic target for HCC treatment.

Novel transcriptional networks regulated by CLOCK in human neurons

“…PRDX3 is the second most interconnected gene in CM2, was confirmed as upregulated with an independent hNP line and alternative shRNA to CLOCK (Supplemental Fig. S9), and has been shown to mediate cell migration in the HepG2 hepatocellular carcinoma cell line (Liu et al 2016). DISC1 is heavily implicated in both the schizophrenia and ASD disease pro-cess, and a mutant form of this gene has been linked to abnormal neocortical development due to migration defects (Kamiya et al 2005).…”

Systematic Characterization of Prognostic Values of Peroxiredoxin Family in Gastric Cancer

“…According to previous publications, high expression PRDX3 is associated with advanced malignant phenotype and worse prognosis in hepatocellular carcinoma [26], endometrial cancer [27], and medulloblastoma [28]. Besides, serum proteomics-based analysis identified autoantibodies against PRDX3 as potential diagnostic biomarkers in nasopharyngeal carcinoma [29].…”

PRDX3 is associated with metastasis and poor survival in uveal melanoma

“…Overexpression of PRDX3 has been implicated in several cancers, including prostate, breast, hepatocellular, colorectal, lung and nasopharyngeal cancer, suggesting that it supports increased metabolism and protects proliferating cancer cells from apoptosis and chemodestruction 21–28. Chang et al 29 identified PRDX3, via its effects on H 2 O 2 , to be a critical regulator of apoptotic signalling.…”

“…In addition, these proteins are also involved in a range of other cellular roles, including the modulation of cytokine-induced hydrogen peroxide levels, which have been shown to mediate signalling cascades leading to gene expression, cell proliferation, differentiation and apoptosis 18–20. Overexpression of thioredoxin-dependent peroxidase reductase (PRDX3) has been implicated in several cancers, including prostate, breast, hepatocellular, colorectal, lung and nasopharyngeal cancer, suggesting that it supports increased metabolism and protects proliferating cancer cells from apoptosis and chemodestruction 21–28…”