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Correlation of microRNA levels during hypoxia with predicted target mRNAs through genome-wide microarray analysis

DOI: 10.1186/1755-8794-2-15

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Abstract:

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.MicroRNAs (miRNA) are approximately 22-nucleotide, non-coding RNA sequences important in the control of gene expression. They are involved in a variety of cellular processes, including development, cell differentiation, signaling, and tumorigenesis[1], and are believed to represent 1% of the predicted genes in mammalian and nematode genomes[2,3]. Mammals in general (and primates in particular) appear to have a large number of miRNAs not found in other animal orders[2], suggesting that many functional miRNAs may have emerged during recent evolutionary periods. According to current functional and predictive models, each miRNA regulates multiple genes during differentiation and/or development at the transcription, translation, and posttranslational levels[1,4,5]. However, few of t

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