Associations between microRNA expression and mesenchymal marker gene expression in glioblastoma
Associations between microRNA expression and mesenchymal marker gene expression in glioblastoma
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DOI：
10.1093/neuonc/nos145
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发表时间：
2012-09-01
期刊：
影响因子：
15.9
通讯作者：
Sasaki, Tomio
中科院分区：
文献类型：
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作者：
Ma, Xinlong;Yoshimoto, Koji;Sasaki, Tomio
已经尝试使用基于 microRNA (miRNA) 和信使 RNA (mRNA) 的整合分析将胶质母细胞瘤 (GBM) 细分为临床相关亚型。由于 miRNA 调节多种基因信号通路，因此了解 miRNA-mRNA 相互作用是了解神经胶质瘤生物学的先决条件。然而，这种关联尚未使用高通量综合分析进行彻底检查。为了确定显着的 miRNA-mRNA 相关性，我们使用实时逆转录酶聚合酶链反应选择并量化了 82 个神经胶质瘤（II 级：14、III：16、IV：52）中的特征 miRNA 和 mRNA。定量表达数据被整合到一个分析平台中，评估 miRNA 和 mRNA 之间的表达关系。这 21 种 miRNA 包括 miR-15b、-21、-34a、-105、-124a、-128a、-135b、-184、-196a-b、-200a-c、-203、-302a-d、-363、-367 和 -504。此外，我们还检查了 23 个基因，包括原神经标记（DLL3、BCAN 和 OLIG2）、间充质标记（YKL-40、CD44 和 Vimentin）、癌症干细胞相关标记和受体酪氨酸激酶基因。原发性 GBM 的特征仅在于间充质标记物的上调，而继发性 GBM 的特征在于间充质标记物 miR-21 和 -34a 的显着下调，以及原神经标记物和 miR-504 的上调。统计分析显示，miR-128a、-504、-124a和-184的表达均与GBM中间充质标志物的表达呈负相关。我们对 miR-128a 和 -504 作为抑制剂的功能分析表明，抑制 miR-128a 和 -504 增加了胶质母细胞瘤细胞系中间充质标志物的表达。 GBM 中的间充质信号传导可能受到 miR-128a 和 -504 的负向调节。
The subclassification of glioblastoma (GBM) into clinically relevant subtypes using microRNA (miRNA)- and messenger RNA (mRNA)-based integrated analysis has been attempted. Because miRNAs regulate multiple gene-signaling pathways, understanding miRNA-mRNA interactions is a prerequisite for understanding glioma biology. However, such associations have not been thoroughly examined using high-throughput integrated analysis. To identify significant miRNA-mRNA correlations, we selected and quantified signature miRNAs and mRNAs in 82 gliomas (grade II: 14, III: 16, IV: 52) using real-time reverse-transcriptase polymerase chain reaction. Quantitative expression data were integrated into a single analysis platform that evaluated the expression relationship between miRNAs and mRNAs. The 21 miRNAs include miR-15b, -21, -34a, -105, -124a, -128a, -135b, -184, -196a-b, -200a-c, -203, -302a-d, -363, -367, and -504. In addition, we examined 23 genes, including proneural markers (DLL3, BCAN, and OLIG2), mesenchymal markers (YKL-40, CD44, and Vimentin), cancer stem cell-related markers, and receptor tyrosine kinase genes. Primary GBM was characterized exclusively by upregulation of mesenchymal markers, whereas secondary GBM was characterized by significant downregulation of mesenchymal markers, miR-21, and -34a, and by upregulation of proneural markers and miR-504. Statistical analysis showed that expression of miR-128a, -504, -124a, and -184 each negatively correlated with the expression of mesenchymal markers in GBM. Our functional analysis of miR-128a and -504 as inhibitors demonstrated that suppression of miR-128a and -504 increased the expression of mesenchymal markers in glioblastoma cell lines. Mesenchymal signaling in GBM may be negatively regulated by miR-128a and -504.