miRNA bioinformatics and pathway analysis

The microRNA (miRNA) mode of action is cooperative in many different ways, leading to an intricate network of coregulations, interactions, and competitive effects on gene target regulations. It is widely known that cells express multiple miRNAs at the same time, a single gene can be targeted by multiple miRNAs and different types of mRNAs competitively act as decoys for miRNAs. Synergistic activity was highlighted by an analysis of the chromosomal distribution of miRNAs in relation to the studied pathology: clustered miRNAs (multiple miRNAs that share the same promoter because they were originated by a long primary transcript) are not only coexpressed but also act in concerted ways. Moreover, experimental evidence demonstrated that, although miRNAs downregulate gene expressions locally, considering a global signaling pathway their function is not necessary repressive but it is dependent on the contextual topology of the pathway. In this scenario, the study of the direct targets of a miRNA, considered as entities isolated from the general context, gives only a partial information regarding miRNA function. To have a holistic perspective of miRNA functions the interactions within the wide and intricate molecular network in which miRNA exploit their action has to be considered. Here we review some of the bioinformatic tools and computational strategies based on pathway and network analyses to infer miRNA functions.