The review articles in this issue provide an improved appreciation for microRNA (miRNA) as an essential feature of lineage commitment and regulatory guidance during tissue development that, when absent or hampered, often lead to disease states. In the coming years, there is much to be learned about adaptive (and maladaptive) states by examining how the expression of miRNAs is influenced by the genetic architecture of miR genes, clusters, and mirtrons, as well as miRNA polymorphism and polymorphism in their mRNA targets. We are also introduced to several modes of miRNA regulation (negative feedback, positive feedback, and cross regulatory) that monitor, modulate, or resolve signaling pathways in a variety of biologic processes that include sepsis response, fibrosis, acute exercise, and steroid biology. Perhaps the homeostasis or micromanagement of these miRNA regulatory systems, when perturbed, arrive at new stable networked interactions that have an undesired effect of promoting or antagonizing disease severity and cancer progression. Clearly, a better understanding of these miRNA regulatory networks, as well as improved therapeutic tools for guiding miRNA expression and their targets toward desired outcomes, will be the subject of many advances in miRNA biology over the coming years.
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