Identifying the differentially expressed microRNAs in autoimmunity: A systemic review and meta-analysis

The evidence indicates that microRNAs (miRNAs) can regulate gene expression and play an important role in the pathogenesis of autoimmune diseases, yet studies on expression profiles of miRNAs are still inconclusive. Our objective is to identify miRNAs that demonstrate enduring differential expression on autoimmune diseases. A systemic review and meta-analysis were performed by analysing the expression profile of miRNAs in several types of autoimmune disease, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and type-1 diabetes (T1D). Several most significant differentially expressed miRNAs were identified and showed significant deregulation in autoimmune diseases. The most compelling results for SLE were with miR-21, miR-148a, miR-223, miR-125b in blood and miR-26a in kidney samples, for RA, miR-21, miR-24, miR-26a, miR-155 and miR-223 in blood, and for T1D, miR-148a, miR-181a in blood and miR-21, miR-155 in urine samples. Interestingly, some of miRNAs were differentially expressed in more than one autoimmune disease, such as miR-21, miR-26a, miR-155, miR-148a, miR-223. These miRNAs are commonly associated with the immune response and increases in the activity of the immune system and inflammation in specific organs such as skin, joint, lung, and kidney. These miRNAs can potentially be not only good biomarkers for the prediction, diagnosis, but also therapeutic targets in autoimmune diseases.

现有研究证据表明，微小核糖核酸（microRNAs，miRNAs）可调控基因表达，并在自身免疫性疾病的发病机制中发挥关键作用，但当前针对miRNAs表达谱的相关研究仍尚无统一定论。本研究旨在筛选出在自身免疫性疾病中呈现持续差异表达的miRNAs。我们通过系统综述与荟萃分析，对系统性红斑狼疮（systemic lupus erythematosus, SLE）、类风湿关节炎（rheumatoid arthritis, RA）及1型糖尿病（type-1 diabetes, T1D）等多种自身免疫性疾病的miRNAs表达谱展开分析。研究最终筛选出若干差异表达最为显著的miRNAs，且上述miRNAs在自身免疫性疾病中均存在显著的表达失调。针对系统性红斑狼疮的核心结果为：血液样本中的miR-21、miR-148a、miR-223、miR-125b，以及肾脏样本中的miR-26a；针对类风湿关节炎的核心结果为血液样本中的miR-21、miR-24、miR-26a、miR-155及miR-223；针对1型糖尿病的核心结果为血液样本中的miR-148a、miR-181a，以及尿液样本中的miR-21、miR-155。值得注意的是，部分miRNAs在多种自身免疫性疾病中均存在差异表达，例如miR-21、miR-26a、miR-155、miR-148a及miR-223。此类miRNAs通常与免疫应答密切相关，且与皮肤、关节、肺脏、肾脏等特定器官的免疫系统激活及炎症反应增强存在关联。这类miRNAs不仅有望成为自身免疫性疾病预测、诊断的优质生物标志物，还可作为潜在的治疗靶点应用于相关疾病的干预治疗。