Important miRs of Pathways in Different Tumor Types

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. We assume that a network of physical interactions between miRs and genes allows us to determine miRs that influence the expression of whole pathways in different tumor types. Specifically, we represented each pathway by an enrichment score and an array of miRs counting the number of genes in the pathway a given miR can bind. Despite the different nature of the considered tumor types, we obtained a large set of overlapping miRs using a machine-learning algorithm. Such associated miRs were enriched with literature-curated cancer and differentially expressed miRs and also coincided well with clusters of miRs that were experimentally indicated in numerous other cancer types. Focusing on such sets of miRs we observed that interactions with genes in differentially expressed pathways were characterized by massive gains/losses of expression correlations. Such drastic changes of miR and gene expression correlation indicate miR/gene pairs that may play a causal role in the underlying cancers.