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KMID : 0923620140140030138
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Immune Network
2014 Volume.14 No. 3 p.138 ~ p.148
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MicroRNA Regulation in Systemic Lupus Erythematosus Pathogenesis
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Yan Sheng
Yim Lok-Yan
Lu Liwei
Lau Chak Sing
Chan Vera Sau-Fong
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Abstract
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MicroRNAs (miRNAs) are endogenous small RNA molecules best known for their function in post-transcriptional gene regulation. Immunologically, miRNA regulates the differ-entiation and function of immune cells and its malfunction contributes to the development of various autoimmune dis-eases 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 machi-nery 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 re-ported 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 hypo-methylation 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 se-quencing, 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.
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KEYWORD
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MicroRNAs, Systemic Lupus Erythematosus, Autoimmunity
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