Investigation of key miRNAs and target genes in bladder cancer using miRNA profiling and bioinformatic tools
Investigation of key miRNAs and target genes in bladder cancer using miRNA profiling and bioinformatic tools
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DOI：
10.1007/s11033-014-3713-5
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发表时间：
2014-12-01
影响因子：
2.8
通讯作者：
Artan, Sevilhan
中科院分区：
文献类型：
--
作者：
Canturk, Kemal Murat;Ozdemir, Muhsin;Artan, Sevilhan
尽管有几种miRNAs与膀胱癌相关，但对miRNAs的调控网络知之甚少。在这项研究中，我们的目的是构建潜在的网络膀胱癌相关的miRNA及其已知的靶基因，使用miRNA表达谱和生物信息学工具，并调查潜在的关键分子，可能在膀胱癌调控网络中发挥作用。使用微阵列获得总体miRNA表达谱，然后使用两种随机选择的miRNA进行RT-qPCR验证。使用DIANA-TarBase数据库v6.0利用去调节的miRNA的已知靶标。使用DIANA-mirPath软件将去调控的miRNA和靶基因掺入KEGG途径中。为了构建潜在的miRNA调控网络，通过Cytoscape软件可视化三个选定的KEGG通路的重叠部分。最终在27例膀胱癌组织和8例正常尿路上皮组织中共获得19条表达下调的miRNAs，其中5条表达上调，14条表达下调。去调控的miRNAs和已知靶基因的富集结果表明，大多数通路与癌症或细胞信号通路相关。我们确定了构建的网络的枢纽CDK 6、BCL 2、E2 F3、PTEN、MYC、RB和ERBB 3靶基因以及枢纽hsa-let-7 c、hsa-miR-195- 5 p、hsa-miR-141- 3 p、hsa-miR-26 a-5 p、hsa-miR-23 b-3 p和hsa-miR-125 b-5 p miRNA。这些发现为膀胱癌调控网络提供了新的见解，并为我们提供了一个假设，即hsa-let-7 c、hsa-miR-195- 5 p和hsa-miR-125 b-5 p可能与CDK 4和CDK 6基因一起沿着存在于同一膀胱癌通路中。特别是，枢纽miRNA和基因可能是膀胱癌临床的潜在生物标志物。
Despite the association of several miRNAs with bladder cancer, little is known about the miRNAs' regulatory networks. In this study, we aimed to construct potential networks of bladder-cancer-related miRNAs and their known target genes using miRNA expression profiling and bioinformatics tools and to investigate potential key molecules that might play roles in bladder cancer regulatory networks. Global miRNA expression profiles were obtained using microarray followed by RT-qPCR validation using two randomly selected miRNAs. Known targets of deregulated miRNAs were utilized using DIANA-TarBase database v6.0. The incorporation of deregulated miRNAs and target genes into KEGG pathways were utilized using DIANA-mirPath software. To construct potential miRNA regulatory networks, the overlapping parts of three selected KEGG pathways were visualized by Cytoscape software. We finally gained 19 deregulated miRNAs, including 5 ups-and 14 down regulated in 27 bladder-cancer tissue samples and 8 normal urothelial tissue samples. The enrichment results of deregulated miRNAs and known target genes showed that most pathways were related to cancer or cell signaling pathways. We determined the hub CDK6, BCL2, E2F3, PTEN, MYC, RB, and ERBB3 target genes and hub hsa-let-7c, hsa-miR-195-5p, hsa-miR-141-3p, hsa-miR-26a-5p, hsa-miR-23b-3p, and hsa-miR-125b-5p miRNAs of the constructed networks. These findings provide new insights into the bladder cancer regulatory networks and give us a hypothesis that hsa-let-7c, hsa-miR-195-5p, and hsa-miR-125b-5p, along with CDK4 and CDK6 genes might exist in the same bladder cancer pathway. Particularly, hub miRNAs and genes might be potential biomarkers for bladder cancer clinics.