Guimbellot Jennifer S, Erickson Stephen W, Mehta Tapan, Wen Hui, Page Grier P, Sorscher Eric J, Hong Jeong S
Department of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
BMC Med Genomics. 2009 Mar 25;2:15. doi: 10.1186/1755-8794-2-15.
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.
在慢性肺病、坏死性肿瘤和高海拔暴露等情况下，组织中的低氧水平会启动一条信号通路，导致具有缺氧反应元件（HRE）的基因发生活跃转录。本研究的目的是基于现有的miRNA靶标预测工具，调查缺氧后miRNA表达的变化是否可以解释细胞转录组的变化。
为了识别缺氧诱导的变化，我们在HT29细胞中进行了基于mRNA和miRNA芯片的实验，并基于多种靶标预测算法对所得数据集进行了比较分析。迄今为止，很少有研究调查环境扰动对全基因组miRNA水平的影响，或其对mRNA产量的后续影响。
将miRNA与其预测的mRNA靶标进行比较，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表达进行组合调控的初步证据。
靶标预测程序和表达谱分析技术尚未充分体现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源于miRNA与mRNA关系的多方面网络，它们在一个相互关联的系统中共同发挥作用，并处于数百种RNA种类的背景下。本文所述的细胞miRNA和mRNA比较分析方法，将有助于理解全基因组调控反应，并完善miRNA预测算法。
