Abstract
The peroxidase family of peroxiredoxins (PRDXs) plays a vital role in maintaining the intracellular balance of ROS. However, their function in head and neck squamous cell carcinoma (HNSCC) has not been investigated. We therefore explored the value of PRDXs in HNSCC. We found that the expression of PRDX1, PRDX4, and PRDX5 in HNSCC increased while the expression of PRDX2 decreased. Moreover, the high expression of PRDX4/5/6 indicated a poor prognosis. Lower expression of PRDX1/5 was linked to more immune cell infiltration, higher expression of immune-related molecules and a more likely response to anti-PD-1 treatment. Moreover, PRDX5 knockdown inhibited HNSCC cell proliferation, invasion and metastasis and it might promote apoptosis through its antioxidant property. Taken together, our study highlights the potential role of PRDXs in HNSCC. The function of PRDX5 in the development of HNSCC and the formation of the immune microenvironment makes it a promising potential therapeutic target.
Highlights
Head and neck squamous cell carcinoma (HNSCC) is the sixth most frequent tumor, annually accounting for ~ 830 000 new cases and 430 000 deaths worldwide [1]
Compared to the normal tissues, PRDX1, PRDX4 and PRDX5 were significantly upregulated, while PRDX2 was significantly downregulated in head and neck squamous cell carcinoma (HNSCC) tumors (Figure 1A)
Kaplan-Meier survival analysis indicated that higher PRDX3, PRDX4, PRDX5 and PRDX6 expression levels were correlated with poor prognosis (Figure 1C)
Summary
Head and neck squamous cell carcinoma (HNSCC) is the sixth most frequent tumor, annually accounting for ~ 830 000 new cases and 430 000 deaths worldwide [1]. More information on the molecular mechanisms responsible for the progress of HNSCC should be obtained to develop more novel therapeutic targets. Based on the number of cysteines, PRDXs are divided into three categories: typical 2-cysteine peroxiredoxins (PRDX1–PRDX4), atypical 2-cysteine peroxiredoxins (PRDX5), and 1-cysteine peroxiredoxins (PRDX6). These proteins have different functions in antioxidant protection and cellular redox regulation, they share a common molecular mechanism. ROS imbalance is closely associated with tumorigenesis and progression. Moderate ROS generation stimulates cell proliferation and differentiation; excessive ROS induces oxidative damage
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