Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, PR China.
Division of Rheumatology, Allergy and Clinical, Immunology, University of California at Davis School of Medicine, Davis, CA, 95616, USA.
J Autoimmun. 2020 May;109:102438. doi: 10.1016/j.jaut.2020.102438. Epub 2020 Mar 14.
MicroRNAs (miRNAs) are evolutionally conserved, single-stranded RNAs that regulate gene expression at the posttranscriptional level by disrupting translation. MiRNAs are key players in variety of biological processes that regulate the differentiation, development and activation of immune cells in both innate and adaptive immunity. The disruption and dysfunction of miRNAs can perturb the immune response, stimulate the release of inflammatory cytokines and initiate the production of autoantibodies, and contribute to the pathogenesis of autoimmune diseases, including systemic lupus erythmatosus (SLE), rheumatoid arthritis (RA), primary biliary cholangitis (PBC), and multiple sclerosis (MS). Accumulating studies demonstrate that miRNAs, which can be collected by noninvasive methods, have the potential to be developed as diagnostic and therapeutic biomarkers, the discovery and validation of which is essential for the improvement of disease diagnosis and clinical monitoring. Recently, with the development of detection tools, such as microarrays and NGS (Next Generation Sequencing), large amounts of miRNAs have been identified and suggest a critical role in the pathogenesis of autoimmune diseases. Several miRNAs associated diagnostic biomarkers have been developed and applied clinically, though the pharmaceutical industry is still facing challenges in commercialization and drug delivery. The development of miRNAs is less advanced for autoimmune diseases compared with cancer. However, drugs that target miRNAs have been introduced as candidates and adopted in clinical trials. This review comprehensively summarizes the differentially expressed miRNAs in several types of autoimmune diseases and discusses the role and the significance of miRNAs in clinical management. The study of miRNAs in autoimmunity promises to provide novel and broad diagnostic and therapeutic strategies for a clinical market that is still in its infancy.
微小 RNA（miRNAs）是进化上保守的单链 RNA，通过破坏翻译来调节基因表达的转录后水平。miRNAs 是调节固有和适应性免疫中免疫细胞分化、发育和激活的各种生物学过程中的关键参与者。miRNAs 的破坏和功能障碍会扰乱免疫反应，刺激炎症细胞因子的释放并引发自身抗体的产生，并导致自身免疫性疾病的发病机制，包括系统性红斑狼疮（SLE）、类风湿关节炎（RA）、原发性胆汁性胆管炎（PBC）和多发性硬化症（MS）。越来越多的研究表明，miRNAs 可以通过非侵入性方法收集，具有作为诊断和治疗生物标志物的潜力，其发现和验证对于改善疾病诊断和临床监测至关重要。最近，随着检测工具（如微阵列和 NGS（下一代测序））的发展，已经发现了大量的 miRNAs，并表明其在自身免疫性疾病的发病机制中具有重要作用。已经开发出几种与诊断相关的 miRNA 生物标志物并已在临床上应用，但制药行业在商业化和药物输送方面仍面临挑战。与癌症相比，miRNAs 在自身免疫性疾病中的发展还不够成熟。然而，已经有针对 miRNA 的药物被作为候选药物引入并在临床试验中采用。本文全面总结了几种自身免疫性疾病中差异表达的 miRNAs，并讨论了 miRNAs 在临床管理中的作用和意义。miRNAs 在自身免疫中的研究有望为这一仍处于起步阶段的临床市场提供新的广泛的诊断和治疗策略。
