Dissecting the regulation rules of cancer-related miRNAs based on network analysis.

miRNAs (microRNAs) are a set of endogenous and small non-coding RNAs which specifically induce degradation of target mRNAs or inhibit protein translation to control gene expression. Obviously, aberrant miRNA expression in human cells will lead to a serious of changes in protein-protein interaction network (PPIN), thus to activate or inactivate some pathways related to various diseases, especially carcinogenesis. In this study, we systematically constructed the miRNA-regulated co-expressed protein-protein interaction network (CePPIN) for 17 cancers firstly. We investigated the topological parameters and functional annotation for the proteins in CePPIN, especially for those miRNA targets. We found that targets regulated by more miRNAs tend to play a more important role in the forming process of cancers. We further elucidated the miRNA regulation rules in PPIN from a more systematical perspective. By GO and KEGG pathway analysis, miRNA targets are involved in various cellular processes mostly related to cell cycle, such as cell proliferation, growth, differentiation, etc. Through the Pfam classification, we found that miRNAs belonging to the same family tend to have targets from the same family which displays the synergistic function of these miRNAs. Finally, the case study on miR-519d and miR-21-regulated sub-network was performed to support our findings.