Nicotine promotes the development of oral leukoplakia via regulating peroxiredoxin 1 and its binding proteins

Tobacco can induce reactive oxygen species (ROS) production extensively in cells, which is a major risk factor for oral leukoplakia (OLK) development. Peroxiredoxin 1 (Prx1) is a key antioxidant protein, upregulated in a variety of malignant tumors. We previously found that nicotine, the main ingredient of tobacco, promotes oral carcinogenesis via regulating Prx1. The aim of the present study was to screen and identify the Prx1 interacting proteins and investigate the mechanisms of nicotine on the development of OLK. Through liquid chromatography-tandem mass spectrometry combined with bioinformatics analysis, the candidate Prx1 interacting proteins of cofilin-1 (CFL1), tropomyosin alpha-3 chain (TPM3), and serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform (PPP2R1A) were screened in human dysplastic oral keratinocyte cells treated with nicotine. CFL1, TPM3, and PPP2R1A were highly expressed in human OLK tissues. The expression of CFL1 increased and the expression of PPP2R1A decreased in OLK of smokers compared to that in OLK of non-smokers. Nicotine upregulated CFL1 and downregulated PPP2R1A in 4-nitro-quinoline-1-oxide (4NQO)-induced OLK tissues in mice in part dependent on Prx1. Furthermore, the in-situ interaction of CFL1, TPM3, and PPP2R1A with Prx1 were validated in human OLK tissues. Our results suggested that tobacco might promote the development of OLK via regulating Prx1 and its interacting proteins CFL1 and PPP2R1A.

Effects of PRDX1 gene silencing on invasion and migration of human colorectal cancer SW480 cells / 中国免疫学杂志

Objective:To investigate the effects of RNA interference(RNAi)-mediated silencing of Peroxiredoxin 1(PRDX1)gene on the invasion and migration of human colorectal cancer SW480 cells.Methods: Lentiviruses negative control vector and PRDX1 RNAi were transfected respectively into colorectal cancer SW480 cells.The transfected cells were divided into PRDX1 silencing group(si-PRDX1)and negative control group(Vector).The expressions of PRDX1 mRNA and protein in SW480 cells were exa mined by quantitative real-time PCR(qRT-PCR)and immunoblotting(Western blot),respectively.The cell migration and invasion capabilities were evaluated with transwell chamber assay and transwell chamber,respectively.The protein expressions of TIMP-2,MMP-2 and MMP-9 were detected by Western blot.Results: Compared with control group,the expressions of PRDX1 mRNA and protein were significantly decreased in PRDX1 silencing group(P<0.01),PRDX1 gene silencing cell line was successfully constructed.The levels of invasion and migration capacities of SW480 cells transfected with si-PRDX1 were lower than those in the cells transfected with control-siRNA(vector)(P<0.01).The expression of TIMP-2 was significantly increased,while the expressions of MMP-2 and MMP-9 were significantly decreased(P<0.05).Conclusion: Silencing of PRDX1 inhibits the invasion,migration and metastasis of human colorectal cancer SW480 cells by regulating the expressions of TIMP-2,MMP-2 and MMP-9.

Expression and clinical significance of peroxiredoxin Ⅰ in hepatocellular carcinoma with portal vein tumor thrombosis / 中华肝胆外科杂志

Objective To investigate the expression of peroxiredoxin 1 (Prx 1) in hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) and to evaluate the relationship between the expressions of Prx 1 and the postoperative recurrence of this disease. Methods Immunohisto chemistry and Western blotting were performed to examine the expression of Prx 1 protein in 40 patients with HCC with PVTT. Experiments on Sprague Dawley (SD) rat hepatoma model were further carried out to observe the pathological changes of Prx 1 by immunohistochemistry. Clinical outcomes were analyzed to find a correlation between the recurrence and positive rate of Prx 1. Results The expression level of Prx 1 was significantly up-regulated in primary tumor tissues than in tumor thrombosis samples (P＜0.01). Immunohistochemistry results showed that the positive rate of Prx 1 in primary tumor tissues were higher than that in tumor thrombosis. Western blotting confirmed a same trend in the level of Prx 1, the average luminosity of the blots were 1534.2 and 735.6, respectively. There was a significant difference in SD rat hepatoma model, the 4, 8, 12, 16, 20 and 24-week positive rates of Prx 1 in liver tumor tissues were 60%, 80%, 75% ,65%, 40% and 25% respectively. Clinical outcomes showed that the time to first postoperative recurrence of Prx 1 in the primary tumor positive group was significantly higher than that in the negative group (6. 3 vs 3. 7 months, P＜0. 01). Conclusions Prx 1 protein was down-regulated in HCC with PVTT. There was a negative correlation between the expression of Prx 1 and recurrence.