Correlation of microRNA levels during hypoxia with predicted target mRNAs through genome-wide microarray analysis.
Correlation of microRNA levels during hypoxia with predicted target mRNAs through genome-wide microarray analysis.
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DOI：
10.1186/1755-8794-2-15
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发表时间：
2009-03-25
影响因子：
2.7
通讯作者：
Hong JS
中科院分区：
文献类型：
--
作者：
Guimbellot JS;Erickson SW;Mehta T;Wen H;Page GP;Sorscher EJ;Hong JS
在慢性肺病、坏死性肿瘤和高海拔暴露等情况下，组织中的低水平氧气会启动信号传导途径，导致具有缺氧反应元件（HRE）的基因的主动转录。本研究的目的是研究缺氧后miRNA表达的变化是否可以解释基于目前可用的miRNA靶预测工具的细胞转录组的变化。为了确定缺氧诱导的变化，我们在HT29细胞中进行了基于mRNA和miRNA阵列的实验，并基于多靶点预测算法对所得数据集进行了比较分析。迄今为止，很少有研究调查了环境扰动对全基因组miRNA水平的影响，或其对mRNA输出的影响。将miRNAs与预测的mRNA靶点进行比较，结果显示一致性水平低于预期。然而，我们确实发现了miRNA对mRNA表达的组合调控的初步证据。目标预测程序和表达谱分析技术还不能充分代表miRNA介导的基因抑制的复杂性，可能需要新的方法来更好地阐明这些途径。我们的数据表明，miRNA对细胞转录的生理影响来自于miRNA和mRNA关系的多方面网络，它们在一个相互关联的系统中以及在数百种RNA物种的背景下一起工作。本文描述的用于细胞miRNA和mRNA的比较分析的方法将有助于理解全基因组调节响应性和改进miRNA预测算法。
Low levels of oxygen in tissues, seen in situations such as chronic lung disease, necrotic tumors, and high altitude exposures, initiate a signaling pathway that results in active transcription of genes possessing a hypoxia response element (HRE). The aim of this study was to investigate whether a change in miRNA expression following hypoxia could account for changes in the cellular transcriptome based on currently available miRNA target prediction tools. To identify changes induced by hypoxia, we conducted mRNA- and miRNA-array-based experiments in HT29 cells, and performed comparative analysis of the resulting data sets based on multiple target prediction algorithms. To date, few studies have investigated an environmental perturbation for effects on genome-wide miRNA levels, or their consequent influence on mRNA output. Comparison of miRNAs with predicted mRNA targets indicated a lower level of concordance than expected. We did, however, find preliminary evidence of combinatorial regulation of mRNA expression by miRNA. Target prediction programs and expression profiling techniques do not yet adequately represent the complexity of miRNA-mediated gene repression, and new methods may be required to better elucidate these pathways. Our data suggest the physiologic impact of miRNAs on cellular transcription results from a multifaceted network of miRNA and mRNA relationships, working together in an interconnected system and in context of hundreds of RNA species. The methods described here for comparative analysis of cellular miRNA and mRNA will be useful for understanding genome wide regulatory responsiveness and refining miRNA predictive algorithms.
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影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
通讯作者：
Bartel, David P.
影响因子：
14.9
作者：
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通讯作者：
Griffiths-Jones, S
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通讯作者：
Allison, DB
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作者：
Bentwich, I;Avniel, A;Bentwich, Z
通讯作者：
Bentwich, Z
影响因子：
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作者：
DICKMAN, KG;MANDEL, LJ
通讯作者：
MANDEL, LJ