Das Jyotirmoy, Podder Soumita, Ghosh Tapash Chandra
Bioinformatics Centre, Bose Institute, P 1/12, C,I,T, Scheme VII M, Kolkata 700 054, India.
BMC Genomics. 2014 Nov 21;15(1):1010. doi: 10.1186/1471-2164-15-1010.
MicroRNAs are a class of short non-coding RNAs derived from either cellular or viral transcripts that act post-transcriptionally to regulate mRNA stability and translation. In recent days, increasing numbers of miRNAs have been shown to be involved in the development and progression of a variety of diseases. We, therefore, intend to enumerate miRNA targets in several known disease classes to explore the degree of miRNA regulations on them which is unexplored till date.
Here, we noticed that miRNA hits in cancer genes are remarkably higher than other diseases in human. Our observation suggests that UTRs and the transcript length of cancer related genes have a significant contribution in higher susceptibility to miRNA regulation. Moreover, gene duplication, mRNA stability, AREScores and evolutionary rate were likely to have implications for more miRNA targeting on cancer genes. Consequently, the regression analysis have confirmed that the AREScores plays most important role in detecting miRNA targets on disease genes. Interestingly, we observed that epigenetic modifications like CpG methylation and histone modification are less effective than miRNA regulations in controlling the gene expression of cancer genes.
The intrinsic properties of cancer genes studied here, for higher miRNA targeting will enhance the knowledge on cancer gene regulation.
微小RNA是一类短的非编码RNA,来源于细胞或病毒转录本,在转录后发挥作用以调节mRNA的稳定性和翻译。近年来,越来越多的微小RNA已被证明参与多种疾病的发生和发展。因此,我们打算在几种已知的疾病类别中列举微小RNA靶点,以探索迄今为止尚未探索的微小RNA对它们的调控程度。
在这里,我们注意到人类癌症基因中的微小RNA命中数明显高于其他疾病。我们的观察表明,与癌症相关基因的非翻译区(UTRs)和转录本长度对更高的微小RNA调控易感性有显著贡献。此外,基因复制、mRNA稳定性、AREScores和进化速率可能对更多微小RNA靶向癌症基因有影响。因此,回归分析证实AREScores在检测疾病基因上的微小RNA靶点中起最重要作用。有趣的是,我们观察到表观遗传修饰如CpG甲基化和组蛋白修饰在控制癌症基因的基因表达方面不如微小RNA调控有效。
这里研究的癌症基因的内在特性,对于更高的微小RNA靶向作用,将增进对癌症基因调控的认识。