Modeling competing endogenous RNA regulatory networks in glioblastoma multiforme

Recent studies postulated that genes harboring identical microRNA (miRNA) binding sites can crosstalk by competing for a limited pool of the binding miRNAs (the miRNA program), named as the regulation of competing endogenous RNAs (ceRNAs). Incorporating recent biological evidence that ceRNA regulation depends on miRNA program expression levels, we developed, in the present study, a mathematical model for systematically inferring ceRNA regulation that is dependent on expression levels of the miRNA programs from sample-paired mRNA and miRNA expression datasets. Applying the method to analyze glioblastoma datasets, a compact ceRNA regulatory network was constructed. Our data further demonstrated that ceRNA regulation plays an essential role in transient cellular responses to dynamic inter-cellular signals. The findings illuminate mechanism of ceRNA regulation and further provide biological insights into the complex human interactome.