The Study Of Peroxiredoxin ? Deficiency Promotes Skin Tumorigenesis By Inhibiting Keratinocytes Apoptosis

Peroxiredoxin I is an antioxidant enzyme and plays an important role in H2O2-mediated cell signaling. Prdx1 could eliminate intracellular reactive oxygen species and bind with other proteins participating in the process of cell proliferation, differentiation, apoptosis and tumorigenesis. The role of Prdx1 in many tissue tumors has been clarified, but the possible role in the development of skin tumor has not been found yet. In this study, we study the possible role and its mechanism of Prdx1 in the process of of skin tumorigenesis through DMBA/TPA induced skin tumorigenesis model.In this study, we treat back skin of wild-type and Prdx1 knockout mice with DMBA for 1 week and TPA for 20 weeks, measure the diameter of tumors using caliper and count. We also use histopathology methods to observe the difference of skin including skin thickness, number of immunocytes in dermis and apoptotic cells in epidermis. In order to study the mechanisms of how Prdx1 work, we knock down Prdx1 gene in HaCaT cell line to study the exact molecular mechanisms of Prdx1 regulating apoptosis induced by chemicals.Our results showed that compared with wild-type mice, Prdx1 knockout mice developed fewer and smaller tumors. H&E staining results showed that the Prdx1 knockout mice had thinner epidermal layer after 20 weeks' TPA treatment, the same number of immunocytes in dermis and more apoptotic cells after 10 days' TPA treatment compared with wild-type mice. Western blot results showed that epidermis of knockout mice express the same amount of immunity related protein, more apoptosis related protein and fewer anti-apoptosis protein compared with wild-type mice. Results of cell viability detection showed that the Prdx1 knockdown HaCaT cells have lower viability, higher ROS and apoptosis level than control cells. Western blot results of HaCaT cells showed that Prdx1 knockdown HaCaT cells express higher level of Cleavaged caspas3 and lower level of anti-apoptotic protein Bcl-2.The results above indicate that the lack of Prdx1 would elevate ROS level, promote keratinocytes apoptosis and inhibit skin tumorigenesis. Thus, we conclude that Prdx1 could elevate the anti-apoptotic activity of keratinocytes, making gene-mutated cells accumulate in tumor microenvironment, thus promoting the development of skin tumor.