Transcriptome and small RNA deep sequencing reveals deregulation of miRNA biogenesis in human glioma.
Transcriptome and small RNA deep sequencing reveals deregulation of miRNA biogenesis in human glioma.
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DOI：
10.1002/path.4109
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发表时间：
2013-02
影响因子：
7.3
通讯作者：
Nykter, Matti
中科院分区：
文献类型：
--
作者：
Moore, Lynette M.;Kivinen, Virpi;Liu, Yuexin;Annala, Matti;Cogdell, David;Liu, Xiuping;Liu, Chang-Gong;Sawaya, Raymond;Yli-Harja, Olli;Shmulevich, Ilya;Fuller, Gregory N.;Zhang, Wei;Nykter, Matti
致癌和抑制肿瘤的microRNAs(MiRNAs)的表达改变与肿瘤的发生密切相关。然而，人们对这些变化背后的监管机制知之甚少。我们试图阐明miRNA生物发生的放松调控促进了在这些肿瘤中发现的异常miRNA表达谱。利用测序技术对胶质瘤患者样本进行全转录组和小RNA测序，检测前体和成熟miRNAs以直接评估miRNA成熟过程，并询问参与miRNA生物发生主要步骤的基因的表达谱。我们发现，随着从正常脑到低级别再到高级别胶质瘤的发展，大量miRNAs的成熟形式与前体形式的比例增加。在胶质瘤组织中，miRNA生物发生的三个主要步骤(核处理、核质运输和细胞质处理)中每一个步骤所涉及的基因的表达水平都发生了系统的变化。对独立数据集的生存分析表明，参与miRNA成熟的基因的改变与胶质瘤患者的生存相关。用深度测序直接定量miRNA成熟表明，miRNA生物发生途径的失控是胶质瘤发生和发展的标志。
Altered expression of oncogenic and tumor-suppressing microRNAs (miRNAs) is widely associated with tumorigenesis. However, the regulatory mechanisms underlying these alterations are poorly understood. We sought to shed light on the deregulation of miRNA biogenesis promoting the aberrant miRNA expression profiles identified in these tumors. Using sequencing technology to perform both whole-transcriptome and small RNA sequencing of glioma patient samples, we examined precursor and mature miRNAs to directly evaluate the miRNA maturation process, and interrogated expression profiles for genes involved in the major steps of miRNA biogenesis. We found that ratios of mature to precursor forms of a large number of miRNAs increased with the progression from normal brain to low-grade and then to high-grade gliomas. The expression levels of genes involved in each of the three major steps of miRNA biogenesis (nuclear processing, nucleo-cytoplasmic transport, and cytoplasmic processing) were systematically altered in glioma tissues. Survival analysis of an independent data set demonstrated that the alteration of genes involved in miRNA maturation correlates with survival in glioma patients. Direct quantification of miRNA maturation with deep sequencing demonstrated that deregulation of the miRNA biogenesis pathway is a hallmark for glioma genesis and progression.
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影响因子：
5.7
作者：
Karube, Y;Tanaka, H;Takahashi, T
通讯作者：
Takahashi, T
影响因子：
64.8
作者：
He, Lin;He, Xingyue;Hannon, Gregory J.
通讯作者：
Hannon, Gregory J.
DOI：
10.1126/science.1190809
发表时间：
2010-06-25
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cifuentes D;Xue H;Taylor DW;Patnode H;Mishima Y;Cheloufi S;Ma E;Mane S;Hannon GJ;Lawson ND;Wolfe SA;Giraldez AJ
通讯作者：
Giraldez AJ
影响因子：
64.8
作者：
Davis, Brandi N.;Hilyard, Aaron C.;Hata, Akiko
通讯作者：
Hata, Akiko
影响因子：
14.9
作者：
Griffiths-Jones S;Grocock RJ;van Dongen S;Bateman A;Enright AJ
通讯作者：
Enright AJ