Grade-Specific Expression Profiles of miRNAs/mRNAs and Docking Study in Human Grade I-III Astrocytomas
Grade-Specific Expression Profiles of miRNAs/mRNAs and Docking Study in Human Grade I-III Astrocytomas
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人 I-III 级星形细胞瘤中 miRNA/mRNA 的级别特异性表达谱及对接研究
DOI：
10.1089/omi.2011.0064
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发表时间：
2011-10-01
影响因子：
3.3
通讯作者：
Li, Gui-Yuan
中科院分区：
文献类型：
--
作者：
Li, Dan;Chen, Pan;Li, Gui-Yuan
尽管已经鉴定出几种 miRNA 参与胶质母细胞瘤的肿瘤发生，但人们对 miRNA 的整体表达谱及其在恶性肿瘤早期阶段的星形细胞瘤中的功能靶点知之甚少。本研究使用微阵列并行分析正常脑组织样本和I-III级星形细胞瘤中miRNA和mRNA的整体表达，并通过无监督层次聚类获得它们的级别特异性表达谱。还证实miR-107、miR-124、miR-138和miR-149在I-IV级星形细胞瘤中显着下调，并且miR-124和miR-149的过表达抑制胶质母细胞瘤细胞的增殖和迁移。此外，在与失调基因相关的中央生物过程、调控网络和信号通路中发现了等级特异性变化，并定义了假定的功能性 miRNA-mRNA 对的调控网络。总之，我们的结果可能有助于更好地理解星形细胞瘤肿瘤发生和恶性进展的分子机制。
Although several miRNAs have been identified to be involved in glioblastoma tumorigenesis, little is known about the global expression profiles of miRNAs and their functional targets in astrocytomas at earlier stages of malignancy. In this study the global expression of miRNAs and mRNAs in normal brain tissue samples and grade I-III astrocytomas were analyzed parallelly using microarrays, and the grade-specific expression profiles of them were obtained by unsupervised hierarchical clustering. It was also confirmed that miR-107, miR-124, miR-138, and miR-149 were downregulated significantly in grade I-IV astrocytomas, and overexpression of miR-124 and miR-149 inhibited glioblastoma cell proliferation and migration. Furthermore, grade-specific changes were discovered in the central biological processes, regulatory networks, and signaling pathways associated with dysregulated genes, and a regulatory network of putative functional miRNA-mRNA pairs was defined. In conclusion, our results may contribute to a better understanding of the molecular mechanisms involved in astrocytoma tumorigenesis and malignant progression.