Computational identification of microRNAs associated to both epithelial to mesenchymal transition and NGAL/MMP-9 pathways in bladder cancer.
Computational identification of microRNAs associated to both epithelial to mesenchymal transition and NGAL/MMP-9 pathways in bladder cancer.
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DOI：
10.18632/oncotarget.11805
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发表时间：
2016-11-08
期刊：
影响因子：
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通讯作者：
Libra M
中科院分区：
文献类型：
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作者：
Falzone L;Candido S;Salemi R;Basile MS;Scalisi A;McCubrey JA;Torino F;Signorelli SS;Montella M;Libra M
膀胱癌是泌尿道的主要癌症之一。它通常在疾病的晚期被诊断出来。到目前为止，还没有特异性和有效的早期检测生物标志物。膀胱癌的发生发展与上皮间质转化（epithelial-mesenchymal transition， EMT）和肿瘤微环境的参与有关，其中NGAL/MMP-9复合物在膀胱癌中起主要作用。众所周知，microRNAs （miRNAs）表达的变化可能导致基因调控。因此，鉴定与EMT通路和NGAL/MMP-9复合物相关的特异性mirna可能有助于早期检测膀胱癌的发展。基于此，我们评估了包含非编码RNA分析数据的膀胱癌公共数据集中mirna的表达水平。该分析揭示了膀胱癌患者与相关健康对照者之间16组mirna的差异表达。通过miRNA预测工具（mirDIP），确定鉴定的miRNA与EMT基因之间的关系。使用DIANA-mirPath （v.2）软件识别能够调节NGAL和MMP-9基因表达的mirna。本研究结果证明，下调的hsa-miR-145-5p和hsa-miR-214-3p可能调节EMT和NGAL/MMP-9通路的表达。因此，进一步的验证分析可能会证实这些选择的mirna在疾病早期预测膀胱癌发展的有效性。
Bladder cancer is one of the leading cancer of the urinary tract. It is often diagnosed at advanced stage of the disease. To date, no specific and effective early detection biomarkers are available. Cancer development and progression are associated with the involvement of both epithelial-mesenchymal transition (EMT) and tumor microenvironment of which NGAL/MMP-9 complex represents the main player in bladder cancer. It is known that change in microRNAs (miRNAs) expression may result in gene modulation. Therefore, the identification of specific miRNAs associated with EMT pathway and NGAL/MMP-9 complex may be useful to detect the development of bladder cancer at early stages. On this ground, the expression levels of miRNAs in public available datasets of bladder cancer containing data of non-coding RNA profiling was evaluated. This analysis revealed a group of 16 miRNAs differentially expressed between bladder cancer patients and related healthy controls. By miRNA prediction tool (mirDIP), the relationship between the identified miRNAs and the EMT genes was established. Using the DIANA-mirPath (v.2) software, miRNAs, able to modulate the expression of NGAL and MMP-9 genes, were recognized. The results of this study provide evidence that the downregulated hsa-miR-145-5p and hsa-miR-214-3p may modulate the expression of both EMT and NGAL/MMP-9 pathways. Therefore, further validation analyses may confirm the usefulness of these selected miRNAs for predicting the development of bladder cancer at the early stage of the disease.