Expression of PRDX6 Correlates with Migration and Invasiveness of Colorectal Cancer Cells

Abstract

Background/Aims: Colorectal cancer (CRC) is the third most common type of cancer and the second leading cause of cancer-related deaths worldwide. PRDXs are antioxidant enzymes that play an important role in cell differentiation, proliferation and apoptosis and have diverse functions in malignancy development. However, the mechanism of aberrant overexpression of PRDX6 in CRC remains unclear. Methods: Boyden chamber assay, flow cytometry and a lentiviral shRNA targeting PRDX6 and transient transfection with pCMV-6-PRDX6 plasmid were used to examine the role of PRDX6 in the proliferation capacity and invasiveness of CRC cells. Immunohistochemistry (IHC) with tissue array containing 40 paraffin- embedded CRC tissue specimens and Western blot assays were used to detect target proteins. Results: PRDX6 was significantly up-expressed in different comparisons of metastasis of colorectal adenomas in node-positive CRC (P = 0.03). In in vitro HCT-116, PRDX6 silencing markedly suppressed CRC cell migration and invasiveness while also inducing cell cycle arrest as well as the generation of reactive oxygen species (ROS); specific overexpression of PRDX6 had the opposite effect. Mechanistically, the PRDX6 inactivation displayed decreased levels of PRDX6, N-cadherin, β-catenin, Vimentin, Slug, Snail and Twist-1 through the activation of the PI3K/ AKT/p38/p50 pathways, but they were also significantly inhibited by PRDX6 transfectants. There was also increased transcriptional activation of dimethylation of histone H3 lysine 4 (H3K4me3) of PRDX6 promoter via the activation of the PI3K/Akt/NFkB pathways. Conclusion: Our findings demonstrated that PRDX6 expression plays a characteristic growth-promoting role in CRC metastasis. This study suggests that PRDX6 may serve as a biomarker of node-positive status and may have a role as an important endogenous regulator of cancer cell tumorigenicity in CRC. PRDX6 may also be an effective therapeutic target.

Comprehensive analysis of peroxiredoxins expression profiles and prognostic values in breast cancer

“…Last but not least, there is no available research about the exact function of PRDX5 and PRDX6 in BrCa, but overexpression of PRDX5 and prognostic values have been observed in numerous cancers, including ovarian cancer and endometrial cancer [34, 35]. As well, the tumor promoter role of PRDX6 in cancers has also been suggested in colorectal cancer, lung cancer and so on [36, 37]. Although several studies that investigate the role of PRDXs in BrCa have been published, little is known about individual PRDXs expression and their effects on survival of BrCa patients.…”

Knockout of PRDX6 induces mitochondrial dysfunction and cell cycle arrest at G2/M in HepG2 hepatocarcinoma cells

“…We observed changes in proteins involved in G1 and S phases of the cell cycle that point to a successful progression through them with a central role of p27 degradation, p21 inactivation and E2F1 activation. However, previous reports claimed that PRDX6 silencing arrests cell cycle at G1/S by a mechanism dependent on its PLA 2 activity [ 17 , 23 , 68 ]. Therefore, the arrest that we observe at G2/M should be related to its peroxidase activity, instead.…”

Antioxidant protein peroxiredoxin 6 suppresses the vascular inflammation, oxidative stress and endothelial dysfunction in angiotensin II-induced endotheliocyte

“…PRDX6 is expressed in almost all mammalian tissues and is highly expressed in solid organs. PRDX6 silencing markedly suppressed colorectal cancer (CRC) cell migration and invasiveness while also inducing cell cycle arrest as well as the generation of ROS; specific overexpression of PRDX6 had the opposite effect (Huang et al 2018). PRDX6 is more important than other antioxidants under excessive oxidative stress in vivo (Wang et al 2003).…”