Abstract
Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease that afflicts multiple organs, especially kidneys and joints. In addition to genetic predisposition, it is now evident that DNA methylation and microRNAs (miRNAs), the two major epigenetic modifications, are critically involved in the pathogenesis of SLE. DNA methylation regulates promoter accessibility and gene expression at the transcriptional level by adding a methyl group to 5′ cytosine within a CpG dinucleotide. Extensive evidence now supports the importance of DNA hypomethylation in SLE etiology. miRNAs are small, non-protein coding RNAs that play a critical role in the regulation of genome expression. Various studies have identified the signature lupus-related miRNAs and their functional contribution to lupus incidence and progression. In this review, the mutual interaction between DNA methylation and miRNAs regulation in SLE is discussed. Some lupus-associated miRNAs regulate DNA methylation status by targeting the DNA methylation enzymes or methylation pathway-related proteins. On the other hand, DNA hyper- and hypo-methylation are linked with dysregulated miRNAs expression in lupus. Further, we specifically discuss the genetic imprinting Dlk1-Dio3 miRNAs that are subjected to DNA methylation regulation and are dysregulated in several autoimmune diseases, including SLE.
Highlights
Systemic lupus erythematosus (SLE) is a chronic, debilitating, systemic autoimmune disease
Our study found that the upregulation of Dlk1-Dio3 miRNAs in the splenocytes and purified splenic CD4+ T cells and CD19+ B cells of MRL-lpr lupus cells was correlated with DNA hypomethylation in these cells [98]
In SLE, several miRNAs such as miR-21, miR-148a, and miR126 have been implicated in the pathogenesis, which affect DNA methylation by targeting
Summary
Systemic lupus erythematosus (SLE) is a chronic, debilitating, systemic autoimmune disease. While the precise reasons for the female predominance of autoimmune diseases are not fully clear, it could be due to the intrinsic differences in sex chromosomes (XX versus XY), sex hormones (estrogens versus testosterone), and/or differential responses to extrinsic cues such as environmental exposures [8,9]. Epigenetic factors such as DNA methylation and non-coding small RNAs (microRNAs) have been increasingly recognized in recent studies as key contributors to SLE [10,11] and other autoimmune diseases [12,13,14]. We discuss the dysregulation of genetic imprinting Dlk1-Dio miRNAs in autoimmune disease, which may provide us with a new perspective for understanding the epigenetic mechanism and the role of genomic imprinting in autoimmune disease
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