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自身免疫性疾病中 microRNAs 的失调:发病机制、生物标志物和潜在的治疗靶点。

Dysregulation of microRNAs in autoimmune diseases: Pathogenesis, biomarkers and potential therapeutic targets.

机构信息

Department of Dermatology, The Second Xiangya Hospital of Central South University, Hunan Key Laboratory of Medical Epigenomics, 139 Middle Renmin Road, Changsha, Hunan, 410011, China.

Department of Stomatology, The Third Hospital of Changsha, 176 Laodong West Road, Changsha, Hunan, 410015, China.

出版信息

Cancer Lett. 2018 Aug 1;428:90-103. doi: 10.1016/j.canlet.2018.04.016. Epub 2018 Apr 20.

Abstract

MicroRNAs (miRNAs) are small, single-stranded, endogenous non-coding RNAs that repress the expression of target genes via post-transcriptional mechanisms. Due to their broad regulatory effects, the precisely regulated, spatial-specific and temporal-specific expression of miRNAs is fundamentally important to various biological processes including the immune homeostasis and normal function of both innate and adaptive immune response. Aberrance of miRNAs is implicated in the development of various human diseases, especially cancers. Increasing evidence has revealed a dysregulated expression pattern of miRNAs in autoimmune diseases, among which many play key roles in the pathogenesis. In this review we summarize these findings on miRNA dysregulation implicated in autoimmune diseases, focusing on four representative systemic autoimmune diseases, i.e. systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis and dermatomyositis. The causes of the dysregulation of miRNA expression in autoimmune diseases may include genetic and epigenetic variants, and various environmental factors. Further understanding of miRNA dysregulation and its mechanisms during the development of different autoimmune diseases holds enormous potential to bring about novel therapeutic targets or strategies for these complex human disorders, as well as novel circulating or exosomal miRNA biomarkers.

摘要

微小 RNA(miRNA)是一类小的、单链、内源性非编码 RNA,通过转录后机制抑制靶基因的表达。由于其广泛的调控作用,miRNA 的精确调控、空间特异性和时间特异性表达对包括免疫内稳态和固有及适应性免疫反应的正常功能在内的各种生物学过程至关重要。miRNA 的失常与多种人类疾病的发生,尤其是癌症的发生有关。越来越多的证据表明,miRNA 在自身免疫性疾病中的表达出现失调,其中许多在发病机制中发挥关键作用。在这篇综述中,我们总结了 miRNA 失调与自身免疫性疾病相关的研究结果,重点关注四种代表性的系统性自身免疫性疾病,即系统性红斑狼疮、类风湿关节炎、系统性硬皮病和皮肌炎。自身免疫性疾病中 miRNA 表达失调的原因可能包括遗传和表观遗传变异以及各种环境因素。进一步了解不同自身免疫性疾病中 miRNA 失调及其机制,有可能为这些复杂的人类疾病带来新的治疗靶点或策略,以及新的循环或外泌体 miRNA 生物标志物。

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