Dual tumor-suppressors miR-139-5p and miR-139-3p targeting matrix metalloprotease 11 in bladder cancer.

Dual tumor-suppressors miR-139-5p and miR-139-3p targeting matrix metalloprotease 11 in bladder cancer.
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DOI:
10.1111/cas.13002
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发表时间:
2016-09
期刊:
影响因子:
5.7
通讯作者:
Enokida H
Enokida H
中科院分区:
医学2区
文献类型:
--
作者:
Yonemori M;Seki N;Yoshino H;Matsushita R;Miyamoto K;Nakagawa M;Enokida H

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我们最近通过深度测序对膀胱癌(BC)的microRNA(miRNA)表达特征的研究显示,两种miRNA,microRNA-139 - 5 p/microRNA-139 - 3 p在BC组织中显著下调。本研究的目的是研究这些miRNA的功能作用及其对BC细胞中癌症网络的调节。使用成熟miRNA或小干扰RNA(siRNA)的转染进行BC细胞的功能测定。应用全基因组基因表达分析、计算机模拟分析和双荧光素酶报告基因测定来鉴定miRNA靶标。采用Kaplan-Meier法评估miRNA及其靶基因的表达与总生存期的关系。功能获得研究表明,miR-139 - 5 p和miR-139 - 3 p显著抑制BC细胞的细胞迁移和侵袭。基质金属蛋白酶11基因(MMP 11)被鉴定为miR-139 - 5 p和miR-139 - 3 p的直接靶点。Kaplan-Meier生存曲线显示MMP 11表达越高,BC患者生存期越短(P = 0.029)。在BC细胞中,下调的miR-139 - 5 p或miR-139 - 3 p增强了BC细胞的迁移和侵袭。MMP 11受这些miRNA的直接调控,可能是BC患者生存的良好预后标志物。
Our recent study of the microRNA (miRNA) expression signature of bladder cancer (BC) by deep‐sequencing revealed that two miRNA, microRNA‐139‐5p/microRNA‐139‐3p were significantly downregulated in BC tissues. The aim of this study was to investigate the functional roles of these miRNA and their modulation of cancer networks in BC cells. Functional assays of BC cells were performed using transfection of mature miRNA or small interfering RNA (siRNA). Genome‐wide gene expression analysis, in silico analysis and dual‐luciferase reporter assays were applied to identify miRNA targets. The associations between the expression of miRNA and its targets and overall survival were estimated by the Kaplan–Meier method. Gain‐of‐function studies showed that miR‐139‐5p and miR‐139‐3p significantly inhibited cell migration and invasion by BC cells. The matrix metalloprotease 11 gene (MMP11) was identified as a direct target of miR‐139‐5p and miR‐139‐3p. Kaplan–Meier survival curves showed that higher expression of MMP11 predicted shorter survival of BC patients (P = 0.029). Downregulated miR‐139‐5p or miR‐139‐3p enhanced BC cell migration and invasion in BC cells. MMP11 was directly regulated by these miRNA and might be a good prognostic marker for survival of BC patients.
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