The Role of MicroRNAs in Autoimmune Diseases with Skin Involvement

Abstract

MicroRNAs (miRNAs) are small non-coding RNA molecules that negatively modulate gene expression by binding to the 3' untranslated region (UTR) of target messenger RNAs (mRNAs), which leads to the degradation or translational repression of their target mRNAs. Previous research on miRNAs has revealed a new paradigm of gene regulations and pathways involved in the pathogenesis of autoimmune disorders and malignant diseases. The roles of miRNAs in cellular processes, including cell differentiation, proliferation, apoptosis and immune functions, are not clearly understood. MiRNAs are easily detected in a variety of sources, including tissues, serum and other body fluids, and this make them a good biological sample for pathogenic studies and disease biomarker development. This review encompasses the current understanding of the roles of miRNAs in autoimmunity and the cellular and molecular mechanisms of miRNAs in various autoimmune diseases (AIMDs). Specifically, we focus on the target genes of miRNAs and the biological processes associated with autoimmune diseases with skin involvement, including systemic lupus erythematosus, psoriasis, systemic sclerosis, Behcet's disease and dermatomyositis. In addition, the diagnostic and therapeutic relevance of miRNAs that are involved in autoimmunity are elucidated to provide information for clinical implications.

Increased miR-155-5p expression in dermal mesenchymal stem cells of psoriatic patients: comparing the microRNA expression profile by microarray

“…miRNA are key regulators of a wide variety of biological processes, including cell development and differentiation, angiogenesis, apoptosis, metabolism, and signal transduction (Ambros, 2004). To date, dozens of miRNA have been implicated in diseases characterized by abnormal immune response, such as cancers and inflammatory or autoimmune disorders such as psoriasis (Sonkoly et al, 2007;O'Connell et al, 2010;Tili et al, 2011;Deng et al, 2015). In this study, dermal MSCs, immune regulatory cells located in the dermis, were analyzed for differentially expressed miRNA and identified 13 (5 up-regulated and 8 down-regulated) that were significant.…”

“…They are key regulators in a number of biological processes, including development, cell differentiation, angiogenesis, apoptosis, metabolism, and signal transduction (Bartel, 2009). To date, dozens of miRNA, including miR-146a, miR-31, miR-155, and miR-21, have been found to differentially expressed in autoimmune disorders such as systemic lupus erythematosus (SLE), psoriasis, and systemic sclerosis (Deng et al, 2015). However, these studies only analyzed peripheral blood mononuclear cell, T cell, epidermal lesion, keratinocyte, serum, and fibroblast samples, but not MSCs, which are important for immune regulation.…”

Epigenetics and Vasculitis: a Comprehensive Review

“…MiRNAs are produced in a multi-step process beginning with transcription of primary miRNA which can occur with nearby genes or independently by RNA polymerase II [27]. Primary miRNA is then converted by the Drosha/Pasha complex into a doublestranded miRNA that is subsequently exported out of the nucleus by Exportin 5.…”

Epigenetics and Systemic Lupus Erythematosus: Unmet Needs

“…DNA methylation, histone modification, and altered miRNA profiling are widely accepted as the key epigenetic mechanisms playing a role in SLE. Table 2 [7][8][9][10][11][12][13][14][15], histone modifications [19][20][21], and miRNA profiling [22][23][24][25][26] were found between SLE patients and normal subjects, the specificity of these findings, i.e., in comparison with nonlupus systemic autoimmune diseases, has not been addressed in a systematic way. Accordingly, their value, as diagnostic tools, is still matter of evaluation.…”

“…Whether epigenetic modifications can be also helpful in characterizing the disease activity or the risk for specific organ damage will be discussed in the next sections. -UV-and drug-induced DNA hypo methylation [9][10][11][12] -DNA hypo methylation correlates with disease activity [13][14][15][16][17][18] Histone modifications including methylation and acetylation/de acetylation -Global H3/H4 hypo acetylation in SLE CD4 + T cells [19] -Abnormal histone acetylation close to IL-17 locus [20,21] miRNA regulation -Abnormal miRNA profile in PBMC, in CD4+ T cells, in plasma and kidney from SLE patients [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] Unmet Needs in SLE…”