The Utility of RNA Triplex Formation in Autoimmune Disease: Identification of Therapeutic Dual Synergistic MicroRNAs in Systemic Lupus Erythematosus—A Bioinformatics Approach

Identifying the complementary microRNAs (miRNAs) through a bio- informatics approach will yield a specified, efficacious therapeutic subset of miRNAs for systemic lupus erythematosus (SLE). The study will focus on identifying the miRNAs capable of inhibiting the production of the following genes by forming RNA triplexes: IL18, MBD2, MBD4, FOXA1, and EBNA2 due to their pivotal roles in SLE pathogenesis on a multi-scale basis. Given the fact that nearly half of the SLE risk loci are EBNA2 bound, wherein 99% of SLE patients are EBV-positive, the study will focus on identifying the miRNAs capable of inhibiting the mRNA EBNA2 from the under-expressed, tumor suppressor-miRNA SLE associated subset in B cells. Several immune cells produce IL-18 in part of promoting inflammation in SLE; particularly, the autoreactivity of T cells in SLE is associated with IL-18 which further necessitates the development of autoantibodies. Moreover, the intersectionality of cancer, virulence and autoimmunity presented in SLE raises the Hippo signaling pathway in consideration; particularly, the role of FOXA1 ERα. As aberrant global DNA hypomethylation in helper T cells hallmarks SLE, the study will consider miRNAs with repressive power upon the overexpressed DNA methylation-modifying genes associated with SLE; namely, MBD2, MBD4. The DNA demethylating enzymes, MBD2 and MBD4, results in the transcript overexpression of the most comprehensively studied SLE epigenetically modified genes: CD70, CD40L, KIR2DL4, and ITGAL. Additional research is warranted to determine the activities of miRNA triplexes and expression levels of the genes in SLE models to validate the deter- mined miRNAs that comprehensively characterize the representatives of host defense mediators in SLE: hsa-miR-590-3p and hsa-miR-129-5p.