The role of microRNAs in glucocorticoid action

Clayton Sa,Clark Ar,Jones Sw,Kurowska-Stolarska M

doi:10.1530/ey.15.8.19

Abstract

Glucocorticoids (GCs) are steroids with profound anti-inflammatory and immunomodulatory activities. Synthetic GCs are widely used for managing chronic inflammatory and autoimmune conditions, as immunosuppressants in transplantation, and as anti-tumor agents in certain hematological cancers. However, prolonged GC exposure can cause adverse effects. A detailed understanding of GCs' mechanisms of action may enable harnessing of their desirable actions while minimizing harmful effects. Here, we review the impact on the GC biology of microRNAs, small non-coding RNAs that post-transcriptionally regulate gene expression. Emerging evidence indicates that microRNAs modulate GC production by the adrenal glands and the cells' responses to GCs. Furthermore, GCs influence cell proliferation, survival, and function at least in part by regulating microRNA expression. We propose that the beneficial effects of GCs may be enhanced through combination with reagents targeting specific microRNAs.

Highlights

Functional interactions between miRNAs and target transcripts are based on limited sequence complementarity
How are functional interactions to be predicted with confidence, and how are subtle effects of individual miRNAs to be experimentally validated without the danger of confirmation bias? How are miRNA-mediated effects on biological processes to be identified and understood when they involve many-to-many rather than one-to-one interactions? These challenges are increasingly being met through improvements in miRNA target prediction algorithms, systems biological approaches, better methodologies, and more widespread adoption of best-practice experimental controls
This field of endeavor is an exciting one, but success is far from certain