AIM: To investigate the expression characteristics of peroxiredoxin 1(PRDX1) m RNA and protein in liver cancer cell lines and tissues.METHODS: The RNA sequencing data from 374 patients with liver cancer were obtained ...AIM: To investigate the expression characteristics of peroxiredoxin 1(PRDX1) m RNA and protein in liver cancer cell lines and tissues.METHODS: The RNA sequencing data from 374 patients with liver cancer were obtained from The Cancer Genome Atlas. The expression and clinical characteristics of PRDX1 m RNA were analyzed in this dataset. The Kaplan-Meier and Cox regression survival analysis was performed to determine the relationship between PRDX1 levels and patient survival. Subcellular fractionation and Western blotting were used to demonstrate the expression of PRDX1 protein in six liver cancer cell lines and 29 paired fresh tissue specimens. After bioinformatics prediction,a putative posttranslational modification form of PRDX1 was observed using immunofluorescence under confocal microscopy and immunoprecipitation analysis in liver cancer cells.RESULTS: The m RNA of PRDX1 gene was upregulated about 1.3-fold in tumor tissue compared with the adjacent non-tumor control(P = 0.005). Its abundance was significantly higher in men than women(P < 0.001). High levels of PRDX1 m RNA were associated with a shorter overall survival time(P =0.04) but not with recurrence-free survival. The Cox regression analysis demonstrated that patients with high PRDX1 m RNA showed about 1.9-fold increase of risk for death(P = 0.03). In liver cancer cells,PRDX1 protein was strongly expressed with multiple different bands. PRDX1 in the cytosol fraction existed near the theoretical molecular weight,whereas two higher molecular weight bands were present in the membrane/organelle and nuclear fractions. Importantly,the theoretical PRDX1 band was increased,whereas the high molecular weight form was decreased in tumor tissues. Subsequent experiments revealed that the high molecular weight bands of PRDX1 might result from the post-translational modification by small ubiquitin-like modifier-1(SUMO1).CONCLUSION: PRDX1 was overexpressed in the tumor tissues of liver cancer and served as an independent poor prognostic factor for overall survival. PRDX1 can be modified by SUMO to play specific roles in hepatocarcinogenesis.展开更多
基金Supported by State Key Project for Infectious Diseases,No.2013ZX10002009 and No.2012ZX10002-017State Key Project for Basic Research,No.2014CBA02001 and No.2014CBA02002+1 种基金National High-tech R and D Program,No.2012AA020206Natural Science Foundation of China,No.81071789 and No.81321091
文摘AIM: To investigate the expression characteristics of peroxiredoxin 1(PRDX1) m RNA and protein in liver cancer cell lines and tissues.METHODS: The RNA sequencing data from 374 patients with liver cancer were obtained from The Cancer Genome Atlas. The expression and clinical characteristics of PRDX1 m RNA were analyzed in this dataset. The Kaplan-Meier and Cox regression survival analysis was performed to determine the relationship between PRDX1 levels and patient survival. Subcellular fractionation and Western blotting were used to demonstrate the expression of PRDX1 protein in six liver cancer cell lines and 29 paired fresh tissue specimens. After bioinformatics prediction,a putative posttranslational modification form of PRDX1 was observed using immunofluorescence under confocal microscopy and immunoprecipitation analysis in liver cancer cells.RESULTS: The m RNA of PRDX1 gene was upregulated about 1.3-fold in tumor tissue compared with the adjacent non-tumor control(P = 0.005). Its abundance was significantly higher in men than women(P < 0.001). High levels of PRDX1 m RNA were associated with a shorter overall survival time(P =0.04) but not with recurrence-free survival. The Cox regression analysis demonstrated that patients with high PRDX1 m RNA showed about 1.9-fold increase of risk for death(P = 0.03). In liver cancer cells,PRDX1 protein was strongly expressed with multiple different bands. PRDX1 in the cytosol fraction existed near the theoretical molecular weight,whereas two higher molecular weight bands were present in the membrane/organelle and nuclear fractions. Importantly,the theoretical PRDX1 band was increased,whereas the high molecular weight form was decreased in tumor tissues. Subsequent experiments revealed that the high molecular weight bands of PRDX1 might result from the post-translational modification by small ubiquitin-like modifier-1(SUMO1).CONCLUSION: PRDX1 was overexpressed in the tumor tissues of liver cancer and served as an independent poor prognostic factor for overall survival. PRDX1 can be modified by SUMO to play specific roles in hepatocarcinogenesis.