Contrast in aberrant microRNA expression in systemic lupus erythematosus and rheumatoid arthritis: Is microRNA‐146 all we need?

In the current issue of Arthritis & Rheumatism, the article by Tang et al (1) describes their initial experiments comparing RNA samples from isolated peripheral blood mononuclear cells (PBMCs) obtained from patients with systemic lupus erythematosus (SLE) and controls by microRNA (miRNA) profiling of 156 miRNA species. The majority of data presented follow up on the finding that microRNA-146 (miR-146) was underexpressed in SLE. The apparent interest in miR-146 is partly because it is a known negative regulator of the type I interferon (IFN) and Toll-like receptor 4 (TLR-4) signaling pathway. Thus, underexpression of miR-146 clearly may contribute to the disease activity of SLE because the elevated IFN is believed to correlate with disease activity. Since IFN plays a critical role in the development of lupus in animal models and since the development of lupus in non–rheumatic disease patients following treatment with IFN has been reported, miR-146 may also contribute to the development of disease. The miRNA are ~22-nucleotide noncoding RNA molecules that function in the posttranscriptional regulation of ~30% of messenger RNAs (mRNA) by binding to their 3′-untranslated region (3′-UTR), thus targeting them for degradation or translational repression. Currently, miRNA are known to regulate cellular processes such as apoptosis, differentiation, cell cycle, and immune functions. To date, the miRNA sequence database lists over 800 predicted miRNA.