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首页> 外文期刊>Journal of cellular biochemistry. >Regulatory roles of miRNA in the human neural stem cell transformation to glioma stem cells
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Regulatory roles of miRNA in the human neural stem cell transformation to glioma stem cells

机译：miRNA在人类神经干细胞向神经胶质瘤干细胞转化中的调控作用

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To investigate the expressional alternation of microRNAs (miRNA) during the malignant transformation and development of human glioma, we measured miRNA expression profile as well as mRNA expression profile in normal human neural stem cells (hNSCs) and human glioma stem cells (hGSCs). We found 116 miRNA up-regulated and 62 miRNA down-regulated in GSCs. On the other hand, we identified 1,372 mRNA down-regulated, and 1,501 mRNA up-regulated in GSCs compared to those in NSCs. We then analyzed the pathways and the predicted target genes of the miRNAs which differ significantly in expression between GSCs and NSCs using the statistical enrichment methods. These target mRNAs are involved in many cancer-related signaling pathways, such as cell cycle, axon guidance, glioma development, adhesion junction, MAPK and Wnt signaling. Furthermore, we obtained the differently expressed miRNA-target relationships according to the θ value which is used to calculate the regulation extent of miRNA-target and using the databases of miRanda, Targetscans and Pictar. Among the top 10 miRNA-target relationships, hsa-miR-198 and its potential targeted gene DCX and NNAT were selected for validation, and NNAT was found to be the direct target of miR-198. Finally, the functional roles of miR-155-5p and miR-124-3p whose expressions altered significantly between GSCs and NSCs were addressed. Our results provide new clues for the potential mechanisms involved in the origin and development of glioma. Clinically, the altered miRNAs may serve as potential targets and diagnostic tools for novel therapeutic strategies of glioblastoma. J. Cell. Biochem. 115: 1368-1380, 2014.
机译：为了研究人类神经胶质瘤的恶性转化和发展过程中微小RNA（miRNA）的表达变化，我们测量了正常人神经干细胞（hNSCs）和人类神经胶质瘤干细胞（hGSCs）中的miRNA表达谱和mRNA表达谱。我们发现GSC中有116个miRNA上调，而62个miRNA下调。另一方面，与NSC相比，我们在GSC中发现了1,372个mRNA下调，而1,501个mRNA上调。然后，我们使用统计学富集方法分析了在GSC和NSC之间表达差异显着的miRNA途径和预测的靶基因。这些靶mRNA参与许多与癌症相关的信号传导途径，例如细胞周期，轴突引导，神经胶质瘤发展，粘附连接，MAPK和Wnt信号传导。此外，我们根据θ值获得了不同表达的miRNA-靶标关系，用于计算miRNA-靶标的调控程度并使用了miRanda，Targetscans和Pictar的数据库。在前10个miRNA靶标关系中，选择了hsa-miR-198及其潜在的靶基因DCX和NNAT进行验证，并且发现NNAT是miR-198的直接靶标。最后，解决了miR-155-5p和miR-124-3p在GSC和NSC之间表达明显改变的功能角色。我们的结果为神经胶质瘤的起源和发展所涉及的潜在机制提供了新线索。在临床上，改变的miRNA可以作为胶质母细胞瘤新治疗策略的潜在靶标和诊断工具。 J.细胞。生化。 115：1368-1380，2014。

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