Posttranscriptional regulation of FOXO expression: microRNAs and beyond.

Forkhead box, class O (FOXO) transcription factors are major regulators of diverse cellular processes, including fuel metabolism, oxidative stress response and redox signalling, cell cycle progression and apoptosis. Their activities are controlled by multiple posttranslational modifications and nuclear-cytoplasmic shuttling. Recently, post-transcriptional regulation of FOXO synthesis has emerged as a new regulatory level of their functions. Accumulating evidence suggests that this post-transcriptional mode of regulation of FOXO activity operates in response to stressful stimuli, including oxidative stress. Here, we give a brief overview on post-transcriptional regulation of FOXO synthesis by microRNAs (miRNAs) and by RNA-binding regulatory proteins, human antigen R (HuR) and quaking (QKI). Aberrant post-transcriptional regulation of FOXOs is frequently connected with various disease states. We therefore discuss characteristic examples of FOXO regulation at the post-transcriptional level under various physiological and pathophysiological conditions, including oxidative stress and cancer. The picture emerging from this summary points to a diversity of interactions between miRNAs/miRNA-induced silencing complexes and RNA-binding regulatory proteins. Better insight into these complexities of post-transcriptional regulatory interactions will add to our understanding of the mechanisms of pathological processes and the role of FOXO proteins. LINKED ARTICLES: This article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc.