MicroRNAs provide a crucial level of control for cell development and function through their post-transcriptional regulation of gene expression. Their importance is highlighted by their diverse functions in a range of cell types, including immune cells.
Pioneering studies from O’Connell and colleagues have identified two key microRNAs, termed miR-155 and miR-146a, that regulate the immune system, and therefore contribute to inflammatory disease conditions in mammals. The microRNAs lead to inflammation by acting in cells that express them and through secretion of extracellular vesicles that facilitate microRNAs delivery to distal target cells. Specifically, O’Connell and colleagues’ work has defined a link between these immunoregulatory microRNAs and diseases that include cancer, autoimmunity, and metabolic disorders.
miR-155 promotes FLT3-ITD-induced myeloproliferative disease through inhibition of the interferon response. Wallace JA, Kagele DA, Eiring AM, Kim CN, Hu R, Runtsch MC, Alexander M, Huffaker TB, Lee SH, Patel AB, Mosbruger TL, Voth WP, Rao DS, Miles RR, Round JL, Deininger MW, O’Connell RM. Blood. 2017 Jun;129(23):3074.
Anti-inflammatory microRNA-146a protects mice from diet-induced metabolic disease. Runtsch MC, Nelson MC, Lee SH, Voth W, Alexander M, Hu R, Wallace J, Petersen C, Panic V, Villanueva CJ, Evason KJ, Bauer KM, Mosbruger T, Boudina S, Bronner M, Round JL, Drummond MJ, O’Connell RM. PLoS Genet. 2019 Feb;15(2):e1007970.
MicroRNA-155 coordinates the immunological landscape within murine melanoma and correlates with immunity in human cancers. Ekiz HA, Huffaker TB, Grossmann AH, Stephens WZ, Williams MA, Round JL, O’Connell RM. JCI Insight. 2019 Mar;4(6). pii: 126543.