Molecular analysis of pediatric brain tumors identifies microRNAs in pilocytic astrocytomas that target the MAPK and NF-κB pathways.
Molecular analysis of pediatric brain tumors identifies microRNAs in pilocytic astrocytomas that target the MAPK and NF-κB pathways.
复制标题
小儿脑肿瘤的分子分析可鉴定靶向MAPK和NF-κB途径的毛囊星形胶质细胞瘤中的microRNA。
DOI：
10.1186/s40478-015-0266-3
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发表时间：
2015-12-18
影响因子：
7.1
通讯作者：
Sheer D
中科院分区：
文献类型：
--
作者：
Jones TA;Jeyapalan JN;Forshew T;Tatevossian RG;Lawson AR;Patel SN;Doctor GT;Mumin MA;Picker SR;Phipps KP;Michalski A;Jacques TS;Sheer D
毛细胞型星形细胞瘤是生长缓慢的肿瘤，通常发生在小脑或沿沿着下丘脑/视神经通路的中线。毛细胞性星形细胞瘤中最常见的遗传改变激活ERK/MAPK信号转导通路，这是增殖的主要驱动因素，但也被认为会诱导这些肿瘤的衰老。在此，我们对microRNA和基因表达进行了详细的研究，并结合通路分析，以提高我们对毛细胞型星形细胞瘤调控机制的理解。毛细胞型星形细胞瘤被发现与正常脑组织和其他儿科脑肿瘤相比具有独特的microRNA和基因表达谱。在毛细胞星形细胞瘤中发现的几种上调的microRNA被预测靶向ERK/MAPK和NF-κB信号通路以及参与衰老相关炎症和细胞周期控制的基因。此外，IGFBP 7和CEBPB是衰老相关分泌表型（SASP）的转录诱导物，也与衰老和炎症的标志物CDKN 1A（p21）、CDKN 2A（p16）和IL 1B一起上调。这些发现为毛细胞型星形细胞瘤的衰老表型提供了进一步的证据。此外，他们认为ERK/MAPK通路被认为是这些肿瘤的主要驱动因素，不仅受到遗传畸变的调节，还受到microRNA的调节。本文的在线版本（doi：10.1186/s40478-015-0266-3）包含补充材料，可供授权用户使用。
Pilocytic astrocytomas are slow-growing tumors that usually occur in the cerebellum or in the midline along the hypothalamic/optic pathways. The most common genetic alterations in pilocytic astrocytomas activate the ERK/MAPK signal transduction pathway, which is a major driver of proliferation but is also believed to induce senescence in these tumors. Here, we have conducted a detailed investigation of microRNA and gene expression, together with pathway analysis, to improve our understanding of the regulatory mechanisms in pilocytic astrocytomas. Pilocytic astrocytomas were found to have distinctive microRNA and gene expression profiles compared to normal brain tissue and a selection of other pediatric brain tumors. Several microRNAs found to be up-regulated in pilocytic astrocytomas are predicted to target the ERK/MAPK and NF-κB signaling pathways as well as genes involved in senescence-associated inflammation and cell cycle control. Furthermore, IGFBP7 and CEBPB, which are transcriptional inducers of the senescence-associated secretory phenotype (SASP), were also up-regulated together with the markers of senescence and inflammation, CDKN1A (p21), CDKN2A (p16) and IL1B. These findings provide further evidence of a senescent phenotype in pilocytic astrocytomas. In addition, they suggest that the ERK/MAPK pathway, which is considered the major driver of these tumors, is regulated not only by genetic aberrations but also by microRNAs. The online version of this article (doi:10.1186/s40478-015-0266-3) contains supplementary material, which is available to authorized users.