Breast cancer is one of the leading causes of death for women worldwide. Alterations to the gene regulatory programs lead to perturbed gene expression patterns that in turn generate major deregulations in cellular processes in the cancer phenotype. Among the many mechanisms of gene regulation described, micro-RNA regulation is widely understood to have an important role in the onset and development of breast cancer. Identifying the functional implications of micro-RNA regulation may lead to new strategies for the treatment of this disease.
The regulatory relationships between micro-RNAs and genes were modeled as bipartite networks for breast cancer tissues, as well as for healthy mammary tissue, based on co-expression in data from the Cancer Genome Atlas project. Using the topological properties in these networks, we found a set of highly connected and non-redundant micro-RNAs that emerge in the breast cancer context. We hypothesize that these micro-RNAs, which we call Commodore micro-RNAs (Cdre-miRs) are important control points of biological functions through the regulation of the expression of specific sets of genes.
Five Cdre-miRs were identified: miR-190b, let-7i, miR-29b-2, miR-511, and miR-141. Each of these Cdre-miRs regulates an specific set of genes associated to specific processes, respectively: cell structure organization, angiogenesis, motility and migration, cytokine production and leukocyte cell-cell adhesion respectively. Furthermore, concerted effects of mir-511 and let-7i are involved in the emergence of innate immunity regulation. Our findings are supported by previously published experimental evidence. These results lead us to propose Cdre-miRs as important control elements of biological functions perturbed in breast cancer.