MicroRNAs and Toll-like Receptor/Interleukin-1 Receptor Signaling

The discovery of miRNAs has revolutionized the way we examine the genome, RNAproducts, and the regulation of transcription and translation. Their ability to modulate proteinexpression through mRNA degradation and translation repression resulted in avid scientificinterest in miRNAs over the past decade. This research has led to findings that indicatemiRNAs can regulate an array of cellular functions such as cellular apoptosis, proliferation,differentiation, and metabolism. Specifically, the capability of miRNAs to finely-tune geneexpression naturally lends itself to immune system regulation which requires precise controlfor proper activity. In fact, abnormal miRNAs expression is often seen with inflammatorydisorders like rheumatoid arthritis, systemic lupus erthematosus, experimental autoimmuneencephalomyelitis, and inflammatory cancers. As a result, research investigating miRNAsmodulation of immune cell proliferation, differentiation, and cellular signaling has yieldedfruitful results. Specifically, in this review, we will examine the impact of miRNAs on tolllikereceptor (TLRs) and interleukin-1beta (IL-1beta) signaling, which are integral in the properfunctioning of the innate immune system. These signaling pathways share several keydownstream signaling adaptors and therefore produce similar downstream effects such as theproduction of pro-inflammatory cytokines, chemokines, and interferons. This review willexamine in depth the specific interactions of miRNAs with receptors, adaptor molecules, andregulator molecules within these cellular pathways. In addition, we will discuss themodulation of miRNAs' expression by TLR and IL-1R signaling through positive andnegative feedback loops.

via Journal of Hematology & Oncology