MicroRNA Regulation in Systemic Lupus Erythematosus Pathogenesis

Abstract

MicroRNAs (miRNAs) are endogenous small RNA molecules best known for their function in post-transcriptional gene regulation. Immunologically, miRNA regulates the differentiation and function of immune cells and its malfunction contributes to the development of various autoimmune diseases including systemic lupus erythematosus (SLE). Over the last decade, accumulating researches provide evidence for the connection between dysregulated miRNA network and autoimmunity. Interruption of miRNA biogenesis machinery contributes to the abnormal T and B cell development and particularly a reduced suppressive function of regulatory T cells, leading to systemic autoimmune diseases. Additionally, multiple factors under autoimmune conditions interfere with miRNA generation via key miRNA processing enzymes, thus further skewing the miRNA expression profile. Indeed, several independent miRNA profiling studies reported significant differences between SLE patients and healthy controls. Despite the lack of a consistent expression pattern on individual dysregulated miRNAs in SLE among these studies, the aberrant expression of distinct groups of miRNAs causes overlapping functional outcomes including perturbed type I interferon signalling cascade, DNA hypomethylation and hyperactivation of T and B cells. The impact of specific miRNA-mediated regulation on function of major immune cells in lupus is also discussed. Although research on the clinical application of miRNAs is still immature, through an integrated approach with advances in next generation sequencing, novel tools in bioinformatics database analysis and new in vitro and in vivo models for functional evaluation, the diagnostic and therapeutic potentials of miRNAs may bring to fruition in the future.

Toll-like receptors: potential targets for lupus treatment

“…miRNAs work as post-transcriptional regulators by binding to a target sequence located within the 3' UTR of the mRNA, promoting degradation of the mRNA or inhibiting translation of the mRNA. Accumulating studies provide evidence for the connection between the dysregulated miRNA network and excessively activated TLR signaling in SLE, indicating the potential of miRNA as a novel SLE therapeutic [108][109][110] . In this review, we briefly summarize pilot miRNAs involved in SLE therapy.…”

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.…”

Molecular dysfunctions in acute myeloid leukemia revealed by integrated analysis of microRNA and transcription factor

“…specifically, the regulatory networks of AML gene expression are still unclear. miRNAs are small non-protein coding RNA molecules of ~19-25 nucleotides that mediate post-transcriptional regulation of gene expression level (9). Pri-miRNAs are transcribed by RNA polymerase II and subsequently processed by the Drosha-DGCR8 enzyme complex in the nucleus to form ~70 nt hairpin pre-miRNAs.…”