Integrated Analysis of microRNA Targets Reveals New Insights into Transcriptional-Posttranscriptional Regulatory Cross-Talk

It is becoming increasingly clear that microRNAs are key players in gene regulatory networks, by modulating gene expression at post-transcriptional level. Their involvement in almost all cellular processes has anticipated their role in diseases, with several microRNA-based therapeutics currently undergoing clinical testing. Despite their undeniable relevance and the substantial body of literature demonstrating their role in cancer and other pathologies, the identification of functional interactions is still challenging. Several resources have been developed to address this issue, by gathering information from the literature, following different criteria and reliability scores. In the present study, we have built a network of verified microRNA-mRNA interactions by integrating strong-evidence couples from different resources. We have analysed the resulting network and compared cohorts of co-regulated genes. The results clearly show that hub genes are highly enriched of transcription factors and regulatory proteins, strongly suggesting a cross-talk and a combinatorial effect between transcriptional and post-transcriptional gene control. Data analysis also reveals that several microRNAs control multiple targets involved in the same pathway or biological process, likely contributing in coordinating the levels of the proteins.