Exosome-derived microRNAs contribute to prostate cancer chemoresistance
Exosome-derived microRNAs contribute to prostate cancer chemoresistance
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外泌体衍生的 microRNA 有助于前列腺癌化疗耐药
DOI：
10.3892/ijo.2016.3560
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发表时间：
2016-08-01
影响因子：
5.2
通讯作者：
Zhang, Jian
中科院分区：
文献类型：
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作者：
Li, Jing;Yang, Xin;Zhang, Jian
某些microRNAs(MiRNAs)在癌细胞化疗耐药中起关键作用。然而，外体衍生的miRNAs在发生化疗耐药中的多效性功能仍不清楚。在本研究中，我们旨在利用miRNA表达谱和生物信息学工具，构建来自化疗耐药前列腺癌(PCA)细胞外体的miRNAs及其已知靶基因的潜在网络。用微阵列技术检测miRNA的表达谱。初步筛选了12个miRNAs，并用qRT-PCR进行了验证。利用Diana-TarBase数据库V6.0利用已知的解除调控的miRNAs靶标。利用Diana-mirPath软件将未调控的miRNAs和靶基因整合到KEGG途径中。为了构建潜在的miRNA调控网络，用Cytoscape软件可视化了选定的KEGG途径‘PCA Progment(Hsa05215)’中miRNAs及其Targer基因的重叠部分。我们从两种紫杉醇耐药的前列腺癌细胞(PC3-TXR和DU145-TXR)与其亲本细胞(PC3和DU145)的外体样本中鉴定出29个下调的miRNAs，其中19个上调，10个下调。对解除调控的miRNAs和已知的靶基因的浓缩结果表明，一些途径与几个关键的细胞信号途径相关。我们发现Hub hsa-miR3176、-141-3p、-5004-5p、-16-5p、-3915、-488-3p、-23c、-3673和-3654是Hub基因雄激素受体(AR)和磷酸和张力蛋白同源物(PTEN)的潜在靶点。HUB基因T细胞因子/淋巴增强因子结合因子4(TCF4)靶基因主要受HUB hsa-miR-32-5、-141-3p、-606、-381和-429调控。这些结果可能提供了PCa耐药与外体调控网络之间的联系，从而使我们认为AR、PTEN和TCF4基因可能是外体miRNAs调控癌细胞化疗耐药的重要基因。
Certain microRNAs (miRNAs) play a key role in cancer cell chemoresistance. However, the pleiotropic functions of exosome-derived miRNAs on developing chemoresistance remain unknown. In the present study, we aimed to construct potential networks of miRNAs, which derived from the exosome of chemoresistant prostate cancer (PCa) cells, with their known target genes using miRNA expression profiling and bioinformatic tools. Global miRNA expression profiles were measured by microarray. Twelve miRNAs were initially selected and validated by qRT-PCR. 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 miRNAs and their targer genes from the selected KEGG pathway 'PCa progression (hsa05215)' were visualized by Cytoscape software. We identified 29 deregulated miRNAs, including 19 upregulated and 10 downregulated, in exosome samples derived from two kinds of paclitaxel resistance PCa cells (PC3-TXR and DU145-TXR) compared with their parental cells (PC3 and DU145). The enrichment results of deregulated miRNAs and known target genes showed that a few pathways were correlated with several critical cell signaling pathways. We found that hub hsa-miR3176, -141-3p, -5004-5p, -16-5p, -3915, -488-3p, -23c, -3673 and -3654 were potential targets to hub gene androgen receptor (AR) and phosphatase and tensin homolog (PTEN). Hub gene T-cell factors/lymphoid enhancer-binding factors 4 (TCF4) target genes were mainly regulated by hub hsa-miR-32-5, -141-3p, -606, -381 and -429. These results may provide a linkage between PCa chemoresistance and exosome regulatory networks and thus lead us to propose that AR, PTEN and TCF4 genes may be the important genes which are regulated by exosome miRNAs in chemoresistance cancer cells.