SIRT2在膀胱尿路上皮癌中的表达、临床意义及其对癌细胞增殖、侵袭和迁移的影响

Expression and clinical significance of SIRT2 in urothelial bladder cancer and its impact on cancer cell proliferation,invasion and migration

目的探讨沉默信息调节因子2(SIRT2)在膀胱尿路上皮癌(UBC)组织中的表达、临床意义及下调SIRT2后对膀胱癌细胞增殖、侵袭及迁移的影响。方法利用免疫组化EnVision法检测SIRT2蛋白在95例膀胱尿路上皮癌组织和39例癌旁组织中的表达,分析其与临床病理学参数的关系。采用RT-qPCR检测膀胱癌细胞系中SIRT2 mRNA的表达,Western blot检测膀胱癌细胞系、12对膀胱癌组织中SIRT2蛋白的表达。利用慢病毒感染稳定下调膀胱癌细胞系T24中的SIRT2基因。CCK8法及细胞集落实验检测细胞增殖;Transwell小室法检测细胞侵袭及迁移能力。结果SIRT2在膀胱尿路上皮癌组织中的阳性表达率为84%(80/95),高于正常尿路上皮组织的5%(2/39)(P<0.05)。SIRT2在高级别尿路上皮癌组表达率为95%(38/40),高于低级别组的76%(42/55)(P<0.05);在肌层侵袭组中表达率为96%(24/25),高于非肌层侵袭组的80%(56/70)(P<0.05)。新鲜膀胱癌组织中SIRT2蛋白表达高于癌旁组织。SIRT2的mRNA及蛋白在膀胱癌细胞系中也均表达上调。在T24细胞中敲减SIRT2,细胞增殖、侵袭及迁移能力均明显下降(P<0.05)。结论SIRT2在膀胱尿路上皮癌中高表达,干扰SIRT2显著抑制膀胱癌细胞增殖、侵袭及迁移。

Objective To investigate the expression and clinical significance of silent information regulator 2(SIRT2)form tissue of urothelial bladder cancer(UBC)and the effects of down-regulation of SIRT2 on the proliferation,invasion and migration of bladder cancer cells.Methods The expression of SIRT2 protein was detected in 95 samples of urothelial bladder cancer tissues and 39 paracancerous tissues using the immunohistochemical EnVision method.Its relationship with clinicopathological parameters was analyzed.The expression of SIRT2 mRNA in bladder cancer cell lines was detected by RT-qPCR,and the expression levels of SIRT2 protein in bladder cancer cell lines,12 pairs of fresh bladder cancer tissues were detected by Western blot.Lentiviral infection was used to stably downregulate the SIRT2 gene in bladder cancer cell line T24.CCK8 and cell colony assays were performed to detect changes in cell proliferation ability and Transwell assay to detect changes in cell invasion and migration activity.Results The positive expression rate of SIRT2 in urothelial bladder cancer tissues was 84%(80/95),which was higher than that in normal uroepithelial tissues(5%,2/39)(P<0.05).The expression rate of SIRT2 was higher in the high-grade uroepithelial cancer group(95%,38/40)than in the low-grade group(76%,42/55)(P<0.05);The expression rate was higher in the muscle-infiltrated group(96%,24/25)than in the non-muscle-infiltrated group(80%,56/70)(P<0.05).Expression of SIRT2 protein was higher in fresh bladder cancer tissues than in normal tissues adjacent to the cancer.Expression of mRNA and protein of SIRT2 were also upregulated in bladder cancer cell lines.Knockdown of SIRT2 in T24 cells resulted in a significant decrease in cell activity of proliferation,invasion and migration(P<0.05).Conclusions SIRT2 is highly expressed in bladder uroepithelial carcinoma,and interfers with SIRT2 significantly and so inhibites bladder cancer cell proliferation,invasion and migration.