Regulation of ITGA3 by the dual-stranded microRNA-199 family as a potential prognostic marker in bladder cancer.
Regulation of ITGA3 by the dual-stranded microRNA-199 family as a potential prognostic marker in bladder cancer.
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DOI：
10.1038/bjc.2017.43
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发表时间：
2017-04-11
影响因子：
8.8
通讯作者：
Enokida H
中科院分区：
文献类型：
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作者：
Sakaguchi T;Yoshino H;Yonemori M;Miyamoto K;Sugita S;Matsushita R;Itesako T;Tatarano S;Nakagawa M;Enokida H
基于对膀胱癌的microRNA(MiRNA)特征的深度测序，我们最近发现，来自同一miRNAs的多个双链成熟miRNAs在膀胱癌中得到了充分的表达，并通过调节共同的靶基因发挥了肿瘤抑制作用。我们对BC的深度测序结果表明，所有miR-199家族成员(miR-199A-3p/-5p和miR-199B-3p/-5p)也都下调。我们假设这些miRNAs可能通过调节共同的靶基因而发挥肿瘤抑制基因的功能。用成熟的miRNA进行BC细胞的功能检测。在电子计算机分析和荧光素酶报告分析中，用来确定这些miRNAs的靶基因。用Kaplan-Meier方法评估癌症基因组图谱(TCGA)数据库中BC患者的总体生存情况。这些miRNAs的修复显著抑制了BC细胞的迁移和侵袭。整合素α3(ITGA3)受这些miRNA直接调控。癌症基因组图谱数据库显示，前miR-199家族(miR-199A-1/-2和miR-199B)低表达的患者总体生存率明显低于前miR-199家族高表达的患者。MIR-199家族miRNAs通过靶向ITGA3在BC细胞中发挥肿瘤抑制作用，可能是预测BC患者生存的良好预后标志物。
Based on the microRNA (miRNA) signature of bladder cancer (BC) by deep sequencing, we recently found that several double-stranded mature miRNAs derived from the same pre-miRNAs were sufficiently expressed and acted as tumour suppressors by regulating common target genes in BC. Our deep-sequencing signature of BC showed that all miR-199 family members (miR-199a-3p/-5p and miR-199b-3p/-5p) were also downregulated. We hypothesised that these miRNAs may function as tumour suppressors by regulating common target genes. Functional assays of BC cells were performed using transfection of mature miRNA. In silico analyses and luciferase reporter analyses were applied to identify target genes of these miRNAs. The overall survival of patients with BC in The Cancer Genome Atlas (TCGA) database was evaluated by the Kaplan–Meier method. Restoration of these miRNAs significantly inhibited cell migration and invasion in BC cells. Integrin α3 (ITGA3) was directly regulated by these miRNAs. The Cancer Genome Atlas database showed that patients with low pre-miR-199 family (miR-199a-1/-2 and miR-199b) expression exhibited significantly poorer overall survival compared with patients with high pre-miR-199 family expression. miR-199 family miRNAs functioned as tumour suppressors in BC cells by targeting ITGA3 and might be good prognostic markers for predicting survival in patients with BC.