环状RNA circ-DHRS3在膀胱癌组织中的表达及对膀胱癌细胞增殖和侵袭能力的影响  

Expression of circular RNA circ-DHRS3 in bladder cancer tissues and its effect on the proliferation and invasion ability of bladder cancer cells

作　　者：胡国森 杨凌博 李小辉 盖强强 HU Guosen;YANG Lingbo;LI Xiaohui;GE Qiangqiang(Department of Urology,Luoyang Central Hospital,Zhengzhou University,Henan Luoyang 471009,China;Department of Urology,Tongji Hospital Affiliated to Huazhong University of Science and Technology,Hubei Wuhan 430030,China)

机构地区：[1]郑州大学附属洛阳中心医院泌尿外科,河南洛阳471009 [2]华中科技大学附属同济医院泌尿外科,湖北武汉430030

出　　处：《现代肿瘤医学》2024年第12期2171-2176,共6页Journal of Modern Oncology

基　　金：国家自然科学基金(编号:82103284);中国博士后科学基金面上项目(编号:2019M662640)。

摘　　要：目的:探讨环状RNA circ-DHRS3在膀胱癌组织中的表达及其对膀胱癌细胞增殖和侵袭的作用机制。方法:应用GEO数据库分析膀胱癌组织中circ-DHRS3的表达水平及其与患者临床分期、生存期的关系。采用实时定量聚合酶链反应(qRT-PCR)法检测circ-DHRS3在膀胱癌细胞系UMUC3、BIU87、T24、J82中的相对表达量。构建circ-DHRS3过表达的稳转株。克隆形成实验和Transwell实验检测circ-DHRS3对膀胱癌T24细胞增殖和侵袭的影响。双荧光素酶报告基因实验验证circ-DHRS3和miR-1275之间的靶向关系。qRT-PCR法检测circ-DHRS3对T24细胞中miR-1275表达的影响。克隆形成实验和Transwell实验检测miR-1275对circ-DHRS3功能的反转作用。Western blot法检测circ-DHRS3对T24细胞中Wnt/β-Catenin分子通路蛋白表达的影响。结果:膀胱癌组织中circ-DHRS3表达降低(P<0.01),并且其表达水平与患者临床分期负相关(P<0.01),circ-DHRS3高表达患者的生存期长于circ-DHRS3低表达患者(P<0.01)。circ-DHRS3在膀胱癌细胞系UMUC3、BIU87、T24、J82中低表达(均P<0.05),circ-DHRS3表达最低的膀胱癌细胞是T24细胞(P<0.01)。与NC组相比,过表达circ-DHRS3后的T24细胞增殖和侵袭能力均降低(均P<0.01)。circ-DHRS3能够靶向结合并抑制miR-1275的表达(P<0.01)。过表达miR-1275可以逆转circ-DHRS3对T24细胞增殖和侵袭的抑制(P<0.01)。与NC组相比,过表达circ-DHRS3后的T24细胞中Wnt/β-Catenin分子通路蛋白Wnt3a、β-catenin、GSK3β、c-myc均表达降低(均P<0.01)。结论:circ-DHRS3通过靶向负调控miR-1275表达,改变Wnt/β-Catenin分子通路活性,抑制膀胱癌细胞的增殖和侵袭能力。Objective:To explore the expression of circular RNA circ-DHRS3 in bladder cancer tissues and its mechanism of action on bladder cancer cell proliferation and invasion.Methods:The GEO database was used to analyze the expression level of circ-DHRS3 in bladder cancer tissues and its relationship with the clinical stage and survival of patients.Real-time quantitative polymerase chain reaction(qRT-PCR)method was used to detect the relative expression of circ-DHRS3 in bladder cancer cell lines UMUC3,BIU87,T24,and J82.A stable transgenic strain overexpressing circ-DHRS3 was constructed.Clone formation assay and Transwell assay were used to detect the effect of circ-DHRS3 on the proliferation and invasion of bladder cancer T24 cells.Dual-luciferase reporter gene experiment verified the targeting relationship between circ-DHRS3 and miR-1275.qRT-PCR method was used to detect the effect of circ-DHRS3 on the expression of miR-1275 in T24 cells.Clone formation assay and Transwell assay were used to detect the reversal effect of miR-1275 on circ-DHRS3 function.Western blot method was used to detect the effect of circ-DHRS3 on the expression of Wnt/β-Catenin molecular pathway proteins in T24 cells.Results:The expression of circ-DHRS3 in bladder cancer tissue was reduced(P<0.01),and its expression level was negatively correlated with the clinical stage of the patients(P<0.01).The survival period of patients with high circ-DHRS3 expression was longer than that of patients with low circ-DHRS3 expression(P<0.01).circ-DHRS3 was lowly expressed in bladder cancer cell lines UMUC3,BIU87,T24,and J82(all P<0.05).The bladder cancer cell with the lowest expression of circ-DHRS3 was T24 cells(P<0.01).Compared with the NC group,the proliferation and invasion abilities of T24 cells after overexpressing circ-DHRS3 were reduced(both P<0.01).circ-DHRS3 can target and inhibit the expression of miR-1275(P<0.01).Overexpression of miR-1275 can reverse the inhibition of T24 cell proliferation and invasion by circ-DHRS3(P<0.01).Compared with the NC g

关 键 词：膀胱癌 circ-DHRS3 miR-1275 细胞增殖 细胞侵袭 

分 类 号：R737.14[医药卫生—肿瘤]