National Center of Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, United States of America.
PLoS Comput Biol. 2013;9(1):e1002883. doi: 10.1371/journal.pcbi.1002883. Epub 2013 Jan 24.
We computationally determined miRs that are significantly connected to molecular pathways by utilizing gene expression profiles in different cancer types such as glioblastomas, ovarian and breast cancers. Specifically, we assumed that the knowledge of physical interactions between miRs and genes indicated subsets of important miRs (IM) that significantly contributed to the regression of pathway-specific enrichment scores. Despite the different nature of the considered cancer types, we found strongly overlapping sets of IMs. Furthermore, IMs that were important for many pathways were enriched with literature-curated cancer and differentially expressed miRs. Such sets of IMs also coincided well with clusters of miRs that were experimentally indicated in numerous other cancer types. In particular, we focused on an overlapping set of 99 overall important miRs (OIM) that were found in glioblastomas, ovarian and breast cancers simultaneously. Notably, we observed that interactions between OIMs and leading edge genes of differentially expressed pathways were characterized by considerable changes in their expression correlations. Such gains/losses of miR and gene expression correlation indicated miR/gene pairs that may play a causal role in the underlying cancers.
我们通过利用不同癌症类型（如脑胶质瘤、卵巢癌和乳腺癌）中的基因表达谱，计算确定了与分子通路显著相关的 miRs。具体来说，我们假设 miRs 和基因之间的物理相互作用的知识表明了重要 miRs（IM）的子集，这些子集对通路特异性富集分数的回归有重要贡献。尽管所考虑的癌症类型的性质不同，但我们发现了具有强烈重叠的 IM 集。此外，对许多通路重要的 IMs 富含文献整理的癌症和差异表达的 miRs。这样的 IM 集也与在许多其他癌症类型中实验表明的 miR 簇很好地吻合。特别是，我们集中研究了在脑胶质瘤、卵巢癌和乳腺癌中同时发现的一组重叠的 99 个总体重要 miRs（OIM）。值得注意的是，我们观察到 OIMs 与差异表达通路的前沿基因之间的相互作用，其表达相关性发生了相当大的变化。这种 miR 和基因表达相关性的增益/损失表明，miR/基因对可能在潜在癌症中起因果作用。
