Architecture of Signature miRNA Regulatory Networks in Cancer Chemoprevention

Abstract

With new high-throughput technologies and superior computational power available for application to current pharmacology research, biomarker discovery has probably entered its most exciting phase to date, especially with the concurrent advent of systems network biology for “big data.” Study of recurrent network motifs in network architecture can inform us better about regulatory pathways in the cellular milieu, more so in complex disease states like cancer. In this review, we focus on the architecture of miRNA networks with emphasis on chemoresistance networks in response to chemotherapeutic drugs, chemoprevention networks modulated by dietary phytochemicals, and novel bifunctional networks comprised of bifunctional miRNAs that operate in both chemoresistance and chemoprevention. Since miRNA cancer networks are very complex, the regulatory architecture in chemoresistance and/or chemoprevention may likely include added dimensions of modulation by epigenetic miRNAs and lncRNAs, which may explain, at least in part, the bifunctionality associated with signature miRNA nodes in these networks in addition to temporal dynamics, spatial localization, and stress conditions in the dynamic networks representing the complex cellular milieu. Collectively, by a perusal of our chemoresistance, chemoprevention, and bifunctional networks, we can gain deeper insights into the architecture of signature miRNA regulatory networks in cancer that will serve as the basis for future dynamic network studies and facilitate the discovery of novel miRNA/target biomarkers for preventive and/or therapeutic intervention in cancer.