miRNAs in Lupus
Researchers at the University of Pennsylvania School of Medicine are investigating the role of miRNAs in the pathogenesis of systemic lupus erythematosus (SLE). “We are currently profiling miRNAs in T and B cells deriving from the lupus-prone tri-congenic mouse model, B6.Sle123,” says Marianthi Kiriakidou, M.D., associate professor.
The miRNA from these mice is compared to that of a control mouse strain. Since the disease in SLE mice evolves as they age, Dr. Kiriakidou says they also study and compare the miRNA signature among younger and older SLE mice. So far, several miRNAs have been identified that are regulated in SLE mice.
Lupus is a systemic autoimmune disease that can potentially affect every organ. “At the molecular level, our understanding of the mechanisms affected in SLE is limited. Changes in the expression of miRNAs, a defected link in the molecular chain that each of these pathways represents, will serve as a marker to trace these pathways, offering new insights into the pathogenesis of lupus.”
In order to further understand what’s occurring on the molecular level, Dr. Kiriakidou says her lab is also focusing on the biology of the miRNAs and proteins of the Argonaute family that associate with miRNAs in forming microRNPs—the functional units in the miRNA pathway. “Proteins that form the microRNPs are the effectors of the microRNA-mediated gene silencing,” she explains. Ongoing studies include in vitro studies using recombinant mouse Ago2, with the goal to characterize the RNA binding and catalytic and translational repressive activity of mammalian Ago2. “Our goal is to probe the function and contribution of miRNAs in an autoimmune disease model,” Dr. Kiriakidou summarizes.
Scientists in the miRNA field believe these molecules hold great promise, as more studies confirm miRNA profiling holds potential to distinguish cancer from normal tissues. Once thought as useless noncoding RNAs, miRNAs are advancing to perhaps revolutionize disease therapeutics and diagnostics. These may well turn out to be the next magic bullet in medicine’s arsenal.