细胞分裂周期蛋白25同源蛋白C调控肾细胞癌进展与舒尼替尼治疗敏感性  

Cell division cyclin 25 homolog C mediates renal cell carcinoma progression and sunitinib sensitivity

作　　者：苗陈岿 吴嘉进 卜恒涛 王增军[1] 刘边疆[1] Miao Chenkui;Wu Jiajin;Bu Hengtao;Wang Zengjun;Liu Bianjiang(Department of Urology,the First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China)

机构地区：[1]南京医科大学第一附属医院泌尿外科,210029

出　　处：《中华实验外科杂志》2022年第7期1341-1344,共4页Chinese Journal of Experimental Surgery

摘　　要：目的探讨细胞分裂周期蛋白25同源蛋白C(CDC25C)对肾细胞癌进展与舒尼替尼治疗敏感性的影响及其机制。方法分析基因本体论(GO)细胞周期数据集与基因表达综合数据库(GEO)肾癌舒尼替尼耐药基因集,结合癌症基因组图谱(TCGA)数据,鉴定出差异表达的CDC25C基因。在Caki-1与786-O细胞系中转染CDC25C小干扰RNA(siRNA)及其阴性对照,通过细胞活性检测、集落形成和Transwell实验分别检测CDC25C对肾癌增殖、迁移和侵袭潜能的影响。通过免疫印迹法检测CDC25C蛋白表达,给予舒尼替尼处理探究CDC25C对肾癌靶向治疗敏感性的影响。Gene Ontology富集分析进一步明确CDC25C潜在的作用通路。采用t检验及Anova-test等进行组间差异分析,Spearman检验进行相关分析,Kaplan-Meier法绘制生存曲线。结果CDC25C在肾癌组织中表达量(0.45±0.54)显著高于正常组织(0.07±0.15),差异有统计学意义(t=0.758,P<0.01)。生存分析显示CDC25C高表达患者中位生存期(63.7个月)显著低于低表达组(91.7个月),差异有统计学意义(Log-rank=9.860,P<0.01)。敲低CDC25C后Caki-1细胞克隆形成数目[(56.33±7.77)个]低于对照组[(111.67±17.50)个,t=4.991,P<0.01]、侵袭细胞数[(81.33±9.02)个]低于对照组[(201.00±18.52)个,t=10.006,P<0.01],舒尼替尼半抑制浓度(IC50)值[(0.35±0.19)μmol/L]也显著低于对照组细胞[(6.73±1.47)μmol/L,t=7.439,P<0.01],786-O细胞趋势一致。结论CDC25C在肾癌中表达增高并促进肿瘤细胞增殖、转移与舒尼替尼耐药性,靶向CDC25C作用轴有望进一步遏制肾癌进展。Objective To investigate the effect and mechanism of cell division cyclin 25 homolog C(CDC25C)on renal cell carcinoma progression and sunitinib sensitivity.Methods The Gene Ontology cell cycle gene set and the GEO sunitinib resistance gene set of renal cell carcinoma were analyzed.Combined with TCGA kidney cancer database,the differentially expressed CDC25C was identified.Small interfering RNA(siRNA)targeting CDC25C,and its negative control(NC)were transfected into Caki-1 and 786-O cell lines.The effects of CDC25C on the proliferation and invasion potential of renal carcinoma were examined by cell viability,colony formation and Transwell assay,respectively.The expression of CDC25C protein was detected by Western blotting,and sunitinib was administered to explore the effect of CDC25C on the sensitivity of targeted therapy for renal cancer.Gene Ontology analysis was performed to clarify the potential mechanism of CDC25C.SPSS 22.0 software was used for analysis.Measurement data were expressed as mean±standard deviation(MEAN±SD).T test and ANova-test were used for inter-group difference analysis,Spearman test was used for correlation analysis,and Kaplan-Meier method was used to draw survival curve.Results The expression of CDC25C in renal carcinoma(0.45±0.54)was significantly higher than that in normal tissues(0.07±0.15),and the difference was statistically significant(Wilcoxon rank sum test=0.758,P<0.01).Survival analysis showed that the median survival of patients with high CDC25C expression(63.7 months)was significantly shorter than that of patients with low CDC25C expression(91.7 months),and the difference was statistically significant(log-rank=9.86,P<0.01).After CDC25C knockdown,the colony number of Caki-1 cell[(56.33±7.77)cells]was less than that of the control group[(111.67±17.50)cells,t=4.991,P<0.01],the number of invasion cells[(81.33±9.02)cells]was less than the control group[(201.00±18.52)cells,t=,10.06 P<0.01],the half maximal inhibitory concentration(IC50)value of sunitinib[(0.35±0.19)μmol/L]wa

关 键 词：细胞分裂周期蛋白25同源蛋白C 肾癌 靶向治疗 

分 类 号：R737.11[医药卫生—肿瘤]