Topological properties of the drug targets regulated by microRNA in human protein-protein interaction network

The investigation of topological properties of proteins in protein-protein interaction network (PPIN) has great potentials to identify basic protein functions and mechanisms of action. Based on human PPIN, previous study has shown that the topological properties of drug targets are significantly distinguished from those of proteins that are not targeted by drugs (non-drug-targets). MicroRNAs (miRNAs) are known to regulate gene expression at the post-transcriptional level. To determine whether the differences in topological properties between drug targets and non-drug-targets are dominated by the proteins that are regulated by miRNA, we divided the drug targets into two sets: those are regulated by miRNA (mir-drug-targets) and those are not regulated by miRNA (non-mir-drug-targets). We compared the probability of interactions and five topological properties among the three types of proteins in human PPIN. Our results demonstrated that mir-drug-targets preferentially interact with other mir-drug-targets and tend to be hub-bottlenecks. However, there was no bias on topological properties between non-mir-drug-targets and non-drug-targets. The same topological features are observed among non-drug targets. These findings indicate that miRNA regulation has an important role in human PPIN, and may be useful in the development of novel drugs.