Peroxiredoxin 2 is upregulated in colorectal cancer and contributes to colorectal cancer cells’ survival by protecting cells from oxidative stress

Abstract

Peroxiredoxin 2 (Prdx2) is a member of the peroxiredoxin family, which is responsible for neutralizing reactive oxygen species. Prdx2 has been found to be elevated in several human cancer cells and tissues, including colorectal cancer (CRC), and it influences diverse cellular processes involving cells' survival, proliferation, and apoptosis, which suggests a possible role for Prdx2 in the maintenance of cancer cell. However, the mechanism by which Prdx2 modulates CRC cells' survival is unknown. The current study aimed to determine the effect of elevated Prdx2 on CRC cells and to further understand the underlying mechanisms. The results of this study showed that Prdx2 was upregulated in CRC tissues compared with the matched noncancer colorectal mucosa tissues and that Prdx2 expression was positively associated with tumor metastasis and the TNM stage. In the LoVo CRC cell line, Prdx2 was upregulated at both the RNA and protein levels compared with the normal FHC colorectal mucosa cell line. In addition, the LoVo CRC cell line was significantly more resistant to hydrogen peroxide (H₂O₂)-induced apoptosis because of a failure to activate pro-apoptotic pathways in contrast to Prdx2 knockdown cells. Suppression of Prdx2 using a lentiviral vector-mediated Prdx2-specific shRNA in the LoVo cell line restored H₂O₂ sensitivity. Our results suggested that Prdx2 has an essential role in regulating oxidation-induced apoptosis in CRC cells. Prdx2 may have potential as a therapeutic target in CRC.

The role of peroxiredoxins in cancer

“…The dual action of PRDX2 in tumorigenesis has been demonstrated in a CRC model. Lu et al (94), in contrast with what was reported by Feng et al (86), demonstrated that PRDX2 overexpression in CRC tissues was strongly correlated with a more aggressive cancer behavior, tumor metastasis and the tumor-node-metastasis (TNM) stage, indicating a possible role for PRDX2 in CRC progression. Taken together, these data suggest that the mechanism by which PRDX2 exerts its oncogenic action is still poorly understood, and further studies are required.…”

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

“…Several studies have indicated that PRDXs overexpression in cancer tissues strongly correlates with a more aggressive cancer behavior, tumor metastasis and the tumor-node-metastasis (TNM) stage, indicating a possible role in tumorigenesis progression [10]. PRDXs contain protein composed of 6 mammalian PRDXs, namely PRDX I to VI [11].…”

PRDX2 protects hepatocellular carcinoma SMMC-7721 cells from oxidative stress

“…Similar to PRDXs, PRDX2 has been demonstrated to form disulfide-linked homodimers during its catalytic cycle (2). The expression of PRDX2 is unregulated in breast cancer, cervical cancer and colorectal cancer (3)(4)(5)(6). By contrast, silencing of PRDX2 occurs in acute myeloid leukemia and malignant melanomas (7,8).…”

“…The pro-tumorigenic role of PRDX2 may be attributed to, at least partially, protecting cells from oxidative stress (3)(4)(5)(6). Under oxidative stress, reactive oxygen species (ROS) also contribute to tumor necrosis factor-α (TNF-α)-induced cell death (9).…”