Peroxiredoxin 2 is essential for maintaining cancer stem cell-like phenotype through activation of Hedgehog signaling pathway in colon cancer

Abstract

Cancer stem cells (CSCs) are a key target for reducing tumor growth, metastasis, and recurrence. Redox status is a critical factor in the maintenance of CSCs, and the antioxidant enzyme Peroxiredoxin 2 (Prdx2) plays an important role in the development of colon cancer. Therefore, we investigated the contribution of Prdx2 to the maintenance of stemness of colon CSCs. Here, we used short-hairpin RNAs and a Prdx2-overexpression vector to determine the effects of Prdx2. We demonstrated that knockdown of Prdx2 reduced the self-renewal and sphere formation and resulted in increased 5-FU-induced apoptosis in human colon CSCs. Prdx2 overexpression induced reversion of the self-renewal and sphere formation. Furthermore, the effects of Prdx2 resulted in an altered expression of stemness associated with the Hh/Gli1 signaling pathway. Finally, knockdown of Prdx2 in CD133+ cells reduced the volume of xenograft tumors in BALB/c-nu mice. Taken together, colon CSCs overexpress Prdx2, which promotes their stem cell properties via the Hh/Gli1 signaling pathway. The results suggest that Prdx2 may be an effective therapeutic target for the elimination of CSCs in colorectal cancer.

Prediction and Validation of Hub Genes Associated with Colorectal Cancer by Integrating PPI Network and Gene Expression Data

“…The samples were frozen immediately and stored until use. Then, quantification of hub genes was performed by real-time PCR as described previously [ 48 ]. For survival analysis, we used the Kaplan-Meier method to analyze the correlation between overall survival and the hub genes, and the log-rank test was used to compare survival curves.…”

Deletion of Peroxiredoxin II Inhibits the Growth of Mouse Primary Mesenchymal Stem Cells Through Induction of the G0/G1 Cell-cycle Arrest and Activation of AKT/GSK3β/β-Catenin Signaling

“…Nitrosylation of PRDX2 can promote cardiac formation of mouse embryonic stem cells through X-box binding protein-1s/phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) signaling pathway (30); PRDX2 has also been shown to regulate the differentiation of embryonic stem cells into neurons (31). Compared with primary stem cells, the regulation of stem cell stemness by PRDX2 comes more from the study of cancer stem cells (6,32). Silencing PRDX2 gene resulted in the decrease of NANOG expression in colon cancer stem cells, and cell proliferation and migration were significantly reduced (6).…”

“…Compared with primary stem cells, the regulation of stem cell stemness by PRDX2 comes more from the study of cancer stem cells (6,32). Silencing PRDX2 gene resulted in the decrease of NANOG expression in colon cancer stem cells, and cell proliferation and migration were significantly reduced (6). The expression of SRY-related high-mobility-group-box protein-2 and octamer-binding transcription factor-4 was down-regulated in PRDX2-silenced Huh7-H-Ras G12V hepatoma cells, and sphere formation efficiency and epithelial-mesenchymal transition were significantly inhibited (6).…”

“…Silencing PRDX2 gene resulted in the decrease of NANOG expression in colon cancer stem cells, and cell proliferation and migration were significantly reduced (6). The expression of SRY-related high-mobility-group-box protein-2 and octamer-binding transcription factor-4 was down-regulated in PRDX2-silenced Huh7-H-Ras G12V hepatoma cells, and sphere formation efficiency and epithelial-mesenchymal transition were significantly inhibited (6). Mechanistic studies showed that PRDX2 can regulate stemness of cancer stem cells through a variety of signaling pathways, which contribute to the maintenance of the cancer stem cell properties of hepatocellular carcinoma via VEGF/EGFR/STAT3 signaling and RAS/FOXM1 signaling (33)(34)(35).…”

Silencing of PRDX2 Inhibits the Proliferation and Invasion of Non-Small Cell Lung Cancer Cells

“…As a key member of PRDXs family, peroxiredoxin 2 (PRDX2) has been reported to scavenge peroxides and reactive oxygen species (ROS) in cells to regulate redox status, thus participating in a variety of cellular biological functions [14][15][16]. Recent studies identify aberrant expression of PRDX2 in several types of cancers and demonstrate that PRDX2 exerts an important role in cell proliferation, death, and drug sensitivity of cancer [17][18][19][20]. For example, it has been indicated that PRDX2 is upregulated in colorectal cancer and exerts a tumor promoting role in the progression of colorectal cancer [21,22].…”