The
aryl hydrocarbon receptor (AhR) is an environmentally responsive
ligand-activated
transcription factor, identified in the '70s for its toxic responses to halogenated
polycyclic aromatic hydrocarbons, such as
dioxin. Recently, AhR has been recognized as engaged in multiple physiological processes in health and diseases, particularly in the immune system, inflammatory response,
tumorigenesis, and cellular differentiation by epigenetic mechanisms involving
miRNAs. However, there is still scarce information about AhR-dependent
miRNA regulation and
miRNA-mediated epigenetic control in pathologies and
therapies. In this review, we explore the mutual regulation of AhR and
miRNA over the last decade of studies since many
miRNAs have
dioxin response elements (DRE) in their
3' UTR, as well as AhR might contain binding sites of
miRNAs.
TCDD is the most used
ligand to investigate the impact of AhR activation, and the immune system is one of the most sensitive of its targets. An association between
TCDD-activated AhR and epigenetic mechanisms like post-transcriptional regulation by
miRNAs, DNA methylation, or
histone modification has already been confirmed. Besides, several studies have shown that AhR-induced miR-212/132 cluster suppresses
cancers, attenuates
autoimmune diseases, and has an anti-inflammatory role in different immune responses by regulating
cytokine levels and immune cells. Together the ever-expanding new AhR roles and the
miRNA therapeutics are a prominent segment among biopharmaceuticals. Additionally, AhR-activated
miRNAs can serve as valuable
biomarkers of diseases, notably
cancer progression or suppression and chemical exposure. Once AhR-dependent gene expression may hinge on the
ligand, cell type, and context singularity, the reviewed outcomes might help contextualize state of the art and support new trends and emerging opportunities in the field.