MiR-133a-3p在膀胱癌中的表达及其分子机制研究

Expression of MiR-133a-3p in Bladder Cancer and its Molecular Mechanism

目的:利用生物信息学方法研究miR-133a-3p在膀胱癌组织中的表达和临床意义,并鉴定其靶基因和信号通路。方法:来自多个公共高通量数据库的514例膀胱癌组织和78例非癌组织样本用于评估miR-133a-3p的表达水平和临床意义。MiR-133a-3p的靶基因用于检测与膀胱癌进展相关的信号通路及其枢纽基因,并进一步验证枢纽基因与miR-133a-3p的相关性。结果:与非癌组织相比,miR-133a-3p在膀胱癌组织中表达显著下调(SMD=-1.604,p=0.015),且对膀胱癌具有鉴别意义(AUC=0.910,95%CI:0.880至0.930),miR-133a-3p高表达的膀胱癌患者预后相对较差(HR=1.383,p=0.030)。不同的患病年龄(t=2.414,p=0.0162)、疾病分期(T分期:t=2.488,p=0.0133;N分期:t=3.153,p=0.0017)、病理等级(t=2.067,p=0.0393)、肿瘤亚型(t=3.118,p=0.0048)的膀胱癌患者之间,其miR-133a-3p表达水平存在显著差异。富集分析结果表明miR-133a-3p的靶基因通过癌症、胞吞、Rap1等信号通路在膀胱癌中发挥影响。通过蛋白互作网络共筛选出9个枢纽基因(EGFR、CLTA、ARPC5、TFRC、NUDT21、FPR3、LAMC1、GNAI3、CAP1),其中CLTA、TFRC、NUDT21、CAP1与miR-133a-3p呈显著负相关。结论:miR-133a-3p在膀胱癌中表达下调且对膀胱癌具有良好的鉴别、预后价值,它可通过多种信号途径影响膀胱癌的进程。

Objective:Using bioinformatics techniques,it is our goal to investigate miR-133a-3p expression in bladder cancer tissues and its clinical relevance,as well as to pinpoint its target genes and signaling pathways.Methods:The expression level and clinical value of miR-133a-3p were assessed using 514 bladder cancer tissue samples and 78 non-cancer tissue samples from various public high-throughput databases.The signaling pathways associated with the progression of bladder cancer and hub genes were found using the miR-133a-3p target genes,and this further confirmed the association between hub genes and miR-133a-3p.Results:In bladder cancer tissues compared to non-cancerous tissues,miR-133a-3p expression was significantly downregulated(SMD=-1.604,p=0.015),and it was significant for diagnosing bladder cancer(AUC=0.910,95%CI:0.880 to 0.930),bladder cancer patients with high expression of miR-133a-3p had a relatively poor prognosis(HR=1.383,p=0.030).Different age at disease(t=2.414,p=0.0162),disease stage(T stage:t=2.488,p=0.0133;N stage:t=3.153,p=0.0017),pathological grade(t=2.067,p=0.0393)and tumor subtypes(t=3.118,p=0.0048),the expression levels of miR-133a-3p were significantly different.The pathway results demonstrated that miR-133a-3p target genes were functionally enriched in the pathways of“cancer cell apoptosis,”“cadherin-bound cell adhesion”and“cytoskeleton formation.”Protein interaction network was used to screen a total of 9 hub genes(EGFR,CLTA,ARPC5,TFRC,NUDT21,FPR3,LAMC1,GNAI3,CAP1),of which CLTA,TFRC,NUDT21,and CAP1 had significantly negative correlations with miR-133a-3p.Conclusion:MiR-133a-3p,a reliable marker and prognostic factor for the disease,is downregulated in bladder cancer.It can affect the progression of bladder cancer through various signaling pathways.