miRNA regulation in the context of functional protein networks: principles and applications

MicroRNAs (miRNAs) are small non-coding endogenous regulatory RNAs that fine-tune gene expression in a wide range of biological processes and diseases. miRNAs exert their function by targeting mRNAs to trigger their degradation or inhibit protein translation. The proteins encoded by the genes targeted by miRNAs may act as key components of cellular networks, thus the use of biological molecular network information for the purposes of elucidating the role of miRNAs in molecular disease mechanism is a key objective in systems biomedicine. The crosstalk layer between miRNA-target networks and functional protein is rich sources of information to explore the function of miRNAs at the system level. Characterizing the influence of miRNAs in the context of the target (protein interactors of the target) is in the early stages with potential to help better understand how miRNAs function within the cellular networks. In this article, the latest research on the cross-talk between miRNAs and protein networks, particularly physical protein interactions and gene regulatory networks is summarized. This article also covers recent research on understanding the biology of miRNAs at the system level and defines principles of miRNA regulation of protein and gene regulatory networks. The second part of the article highlights the promise of considering the protein context of the miRNA target when searching for functional miRNA-target interactions. Some of the applications of integrating protein networks with miRNA-targets that have clinical and functional utility are described.