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目的:探讨泛素特异性蛋白酶53(ubiquitin specific peptidase 53,USP53)在结直肠癌组织中的表达水平及其过表达对人结直肠癌HCT116细胞功能的影响。方法:运用Real-time PCR及IHC方法检测结直肠癌及癌旁组织中USP53的表达情况;利用UCSC CANCER BROWSER提供的TCGA数据库,检测USP53 mRNA表达水平与临床特征及预后的关系;HCT116细胞中瞬时过表达USP53,利用CCK-8及克隆形成实验检测HCT116细胞增殖变化。结果:免疫组化结果显示,USP53在癌旁组织中的表达显著高于肿瘤组织[91.67%(44/48)vs 18.75%(9/48),P<0.01]。癌旁组织中USP53 mRNA水平也高于癌组织[(0.85±0.32)vs(0.46±0.27),P<0.05]。组织中USP53 mRNA表达水平与预后有关,表达越低预后越差(P<0.05)。过表达USP53后,细胞克隆形成数目显著下降[(123±27.22)vs(338±55.24)个,P<0.01];CCK-8实验结果显示,肿瘤细胞增殖受到显著抑制[(0.14±0.01)vs(0.18±0.04),P<0.05;(0.23±0.01)vs(0.32±0.01),P<0.01;(0.45±0.03)vs(0.80±0.05),P<0.01;(0.83±0.03)vs(1.18±0.10),P<0.01]。结论:USP53在结直肠癌中表达下调与不良预后相关,USP53可抑制肿瘤细胞增殖,提示USP53可作为诊断及治疗结直肠癌的新靶标。
Objective: To investigate the expression of ubiquitin-specific peptidase 53 (USP53) in colorectal cancer and its effect on the function of human colorectal cancer HCT116 cells. Methods: Real-time PCR and IHC were used to detect the expression of USP53 in colorectal cancer and its adjacent tissues. The TCGA database provided by UCSC CANCER BROWSER was used to detect the relationship between the expression of USP53 mRNA and the clinical features and prognosis. HCT116 cells were transiently USP53 was overexpressed, and the proliferation of HCT116 cells was detected by CCK-8 and clonogenic assay. Results: The results of immunohistochemistry showed that the expression of USP53 was significantly higher in paracancer tissues than in tumor tissues [91.67% (44/48) vs 18.75% (9/48), P <0.01]. The level of USP53 mRNA in paracancerous tissues was also higher than that in cancer tissues [(0.85 ± 0.32) vs (0.46 ± 0.27), P <0.05]. The expression of USP53 mRNA in the tissue correlated with the prognosis. The lower the expression, the lower the prognosis (P <0.05). The number of cell clone formation was significantly decreased after USP53 was overexpressed [(123 ± 27.22 vs 338 ± 55.24, P <0.01]. The CCK-8 results showed that the proliferation of tumor cells was significantly inhibited [(0.14 ± 0.01) vs (0.18 ± 0.04), P <0.05; (0.23 ± 0.01) vs (0.32 ± 0.01), P <0.01; 0.45 ± 0.03 vs 0.80 ± 0.05, P <0.01; ± 0.10), P <0.01]. Conclusion: The down-regulation of USP53 in colorectal cancer is associated with poor prognosis. USP53 can inhibit the proliferation of tumor cells, suggesting that USP53 may be a new target for the diagnosis and treatment of colorectal cancer.