KPNB1在膀胱癌中的表达及其对膀胱癌细胞增殖和迁移能力的影响  

Expression of KPNB1 in bladder cancer and its role in proliferation and migration of bladder cancer cells

作　　者：嵇宏声 魏万顷 邱建国 王留成 姜福金 张先云 王苏贵 Ji Hongsheng;Wei Wanqing;Qiu Jianguo;Wang Liucheng;Jiang Fujin;Zhang Xianyun;Wang Sugui(Department of Urology,Lianshui People’s Hospital of Kangda College Affiliated to Nanjing Medical University,Huai’an 223400,China;Department of Urology,Huai’an Hospital Affiliated with Xuzhou Medical University,Huai’an 223002,China)

机构地区：[1]南京医科大学康达学院附属涟水人民医院泌尿外科,江苏淮安223400 [2]徐州医科大学附属淮安医院泌尿外科,江苏淮安223002

出　　处：《中华临床医师杂志(电子版)》2024年第11期1044-1053,共10页Chinese Journal of Clinicians(Electronic Edition)

基　　金：江苏省第十六批“六大人才高峰”项目资助(2019-WSW-218);徐州医科大学附属医院发展基金资助项目(XYFY202243,XYFM202245);淮安市自然科学基金资助项目(HAB201730,HAB202117);淮安市基础研究计划(联合专项)卫生健康类科研项目(HABL2023094)

摘　　要：目的基于生物信息学和细胞实验分析核转运蛋白KPNB1(Karyopherinβ1)在膀胱癌中的表达及其作用机制探索。方法从癌症基因图谱数据库(TCGA)、基因综合表达(GEO)数据库和人类蛋白组图谱(THPA)获取KPNB1在膀胱癌组织及正常膀胱组织当中的mRNA与蛋白表达水平,分析KPNB1与膀胱癌患者临床病理特征的相关性及其在膀胱癌不同分期的表达情况,评估KPNB1在膀胱癌中的诊断及预后判断价值。通过细胞实验对KPNB1在膀胱癌中的作用机制进行初步探索。结果在TCGA、GEO和THPA数据库中,KPNB1 mRNA和蛋白水平在膀胱癌组织中明显高于正常膀胱组织。KPNB1与T分期、N分期及肿瘤病理分级显著相关。KPNB1的表达水平可以有效区分膀胱癌组织与正常膀胱组织(AUC=0.758)。KPNB1表达较高患者具有较差的无进展生存。KPNB1过表达组T24细胞增殖水平以及迁移能力显著提高(P<0.05),KPNB1敲低组T24细胞增殖水平以及迁移能力显著下降(P<0.05)。KPNB1敲低组T24肿瘤细胞表达STAT3/LDHA量相对减少(P<0.05),KPNB1过表达膀胱癌细胞内STAT3/LDHA表达量显著增加(P<0.05)。STAT3抑制剂Stattic处理KPNB1过表达组膀胱癌细胞后,细胞内LDHA表达量显著下降(P<0.05)。结论KPNB1在膀胱癌中高表达,且具有较高的诊断及预后判断价值,并通过参与STAT3/LDHA信号通路在膀胱癌中发挥作用。Objective To investigate the expression and role of Karyopherinβ1(KPNB1)in bladder cancer based on bioinformatics analysis and cell studies.Methods KPNB1 mRNA and protein levels in normal prostate tissues and prostate cancer tissues were obtained from the Cancer Genome Atlas(TCGA),Gene Expression Omnibus(GEO),and the Human Protein Atlas(THPA)databases.The correlation between KPNB1 expression and clinicopathological features of bladder cancer patients,and the expression of KPNB1 in different subgroups of bladder cancer tissues were analyzed.The diagnostic and prognostic value of KPNB1 in bladder cancer was evaluated.Combined with GOKEEG signal pathway enrichment analysis,the mechanism of KPNB1 in bladder cancer was preliminarily explored.Cellular studies were performed using T24 cells with KPNB1 knockdown or overexpression.Results Statistical analysis based on the TGGA,GEO,and THPA databases showed that,compared with normal bladder tissues,KPNB1 mRNA and protein levels were increased in bladder cancer tissues and significantly correlated with N stage,T stage,and degree of tumor invasion.The expression of KPNB1 could effectively distinguish bladder cancer tissues from normal tissues(area under the curve=0.758).KPNB1 expression was higher in patients with poor progression-free survival.The proliferation and migration of T24 cells were significantly increased in the KPNB1 overexpressing group(P<0.05),and the proliferation and migration of T24 cells were significantly decreased in the KPNB1 knockdown group(P<0.05).The expression of STAT3/LDHA in T24 cells was relatively reduced in the KPNB1 knockdown group(P<0.05),and the expression of STAT3/LDHA in KPNB1 overexpressing T24 cells was significantly increased(P<0.05).After treating T24 cells in the KPNB1 overexpressing group with the STAT3 inhibitor Stattic,the expression of LDHA significantly decreased(P<0.05).Conclusion KPNB1 is significantly highly expressed in bladder cancer,which is of great diagnostic and prognostic value.KPNB1 plays a role in bladder cancer by p

关 键 词：膀胱癌 核转运蛋白KPNB1 生物信息学 STAT3/LDHA信号通路 

分 类 号：R737.14[医药卫生—肿瘤]