De-regulated microRNAs in pediatric cancer stem cells target pathways involved in cell proliferation, cell cycle and development.
De-regulated microRNAs in pediatric cancer stem cells target pathways involved in cell proliferation, cell cycle and development.
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DOI：
10.1371/journal.pone.0061622
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Hung JY
中科院分区：
文献类型：
--
作者：
Sanchez-Diaz PC;Hsiao TH;Chang JC;Yue D;Tan MC;Chen HI;Tomlinson GE;Huang Y;Chen Y;Hung JY
microRNAs （miRNAs）与许多生物过程的控制有关，其失调与许多癌症有关。近年来，癌症干细胞（CSC）的概念已被应用于包括儿科在内的多种癌症。我们假设，在CSCs部分中解除调控的mirna的共同特征可以解释CSCs中信号通路的中断。使用高通量qPCR方法，我们鉴定了26个CSC相关的差异表达mirna （demir）。利用BCmicrO算法获得865个潜在的CSC相关DEmiR靶点。对这些潜在靶点进行KEGG、Biocarta和Gene Ontology通路和生物过程分析。细胞周期、细胞增殖、p53和tgf - β /BMP四个通路被富集。在细胞系中使用反义寡核苷酸和小干扰RNA敲除hsa-miR-21-5p、hsa-miR-181c-5p和hsa-miR-135b-5p导致CSC部分的消耗和球体形成的损害（CSC替代试验）。我们的研究结果表明，CSC相关的demir及其调节的假定途径可能在儿科癌症的治疗中具有潜在的应用。
microRNAs (miRNAs) have been implicated in the control of many biological processes and their deregulation has been associated with many cancers. In recent years, the cancer stem cell (CSC) concept has been applied to many cancers including pediatric. We hypothesized that a common signature of deregulated miRNAs in the CSCs fraction may explain the disrupted signaling pathways in CSCs. Using a high throughput qPCR approach we identified 26 CSC associated differentially expressed miRNAs (DEmiRs). Using BCmicrO algorithm 865 potential CSC associated DEmiR targets were obtained. These potential targets were subjected to KEGG, Biocarta and Gene Ontology pathway and biological processes analysis. Four annotated pathways were enriched: cell cycle, cell proliferation, p53 and TGF-beta/BMP. Knocking down hsa-miR-21-5p, hsa-miR-181c-5p and hsa-miR-135b-5p using antisense oligonucleotides and small interfering RNA in cell lines led to the depletion of the CSC fraction and impairment of sphere formation (CSC surrogate assays). Our findings indicated that CSC associated DEmiRs and the putative pathways they regulate may have potential therapeutic applications in pediatric cancers.
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