College of Bioinformatics Science and Technology, Department of Neurology, The Affiliated Hospital and Harbin Medical University, Harbin, Heilongjiang 150086, China.
Nucleic Acids Res. 2012 Sep;40(16):7653-65. doi: 10.1093/nar/gks538. Epub 2012 Jun 16.
Accumulating evidence indicates that microRNAs (miRNAs) can function as oncogenes or tumor suppressor genes by controlling few key targets, which in turn contribute to the pathogenesis of cancer. The identification of cancer-related key miRNA-target interactions remains a challenge. We performed a systematic analysis of known cancer-related key interactions manually curated from published papers based on different aspects including sequence, expression and function. Known cancer-related key interactions show more miRNA binding sites (especially for 8mer binding sites), more reliable binding of miRNA to the target region, higher expression associations and broader functional coverage when compared to non-disease-related interactions. Through integrating these sequence, expression and function features, we proposed a bioinformatics approach termed PCmtI to prioritize cancer-related key interactions. Ten-fold cross-validation of our approach revealed that it can achieve an area under the receiver operating characteristic curve of 93.9%. Subsequent leave-one-miRNA-out cross-validation also demonstrated the performance of our approach. Using miR-155 as a case, we found that the top ranked interactions can account for most functions of miR-155. In addition, we further demonstrated the power of our approach by 23 recently identified cancer-related key interactions. The approach described here offers a new way for the discovery of novel cancer-related key miRNA-target interactions.
越来越多的证据表明， microRNAs (miRNAs) 可以通过控制少数关键靶标发挥癌基因或肿瘤抑制基因的作用，进而有助于癌症的发病机制。鉴定与癌症相关的关键 miRNA-靶标相互作用仍然是一个挑战。我们根据序列、表达和功能等不同方面，对已发表论文中人工整理的已知与癌症相关的关键相互作用进行了系统分析。与非疾病相关的相互作用相比，已知与癌症相关的关键相互作用显示出更多的 miRNA 结合位点（特别是 8mer 结合位点）、miRNA 与靶区更可靠的结合、更高的表达相关性和更广泛的功能覆盖。通过整合这些序列、表达和功能特征，我们提出了一种称为 PCmtI 的生物信息学方法来优先考虑与癌症相关的关键相互作用。我们方法的 10 倍交叉验证表明，它可以实现接收者操作特征曲线下面积的 93.9%。随后的一次留一 miRNA 交叉验证也证明了我们方法的性能。以 miR-155 为例，我们发现排名靠前的相互作用可以解释 miR-155 的大部分功能。此外，我们还通过 23 个最近确定的与癌症相关的关键相互作用进一步证明了我们方法的有效性。这里描述的方法为发现新的与癌症相关的关键 miRNA-靶标相互作用提供了一种新方法。
