Sex differences and estrogen regulation of miRNAs in lupus, a prototypical autoimmune disease

Unique dysregulated expression patterns of microRNAs (miRNAs) have been reported in many disease conditions including autoimmune diseases such as systemic lupus erythematosus (SLE). We have recently reported that miRNAs are differentially expressed not only between autoimmune and control mice, but also between male and female lupus-prone mice. This important observation is of potential clinical and experimental significance since females have higher incidence, earlier expression or severity of lupus when compared to their male counterparts. Further, estrogen administration to orchiectomized males accelerates the expression of lupus-related miRNAs and induces unique miRNA signature profile. Understanding the basis of altered miRNAs in autoimmune diseases offers a new paradigm to understand autoimmune diseases, including sex-differential susceptibility. In this review, we summarize miRNA biogenesis and function, and focus on miRNA dysregulation in SLE in the context of sexual bias. Furthermore, the effect of estrogen on epigenetic miRNA regulation in relation to SLE is highlighted.