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RNA（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，但目前针对miRNAs表达谱的相关研究仍未形成统一结论。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表达谱进行了分析。最终鉴定出数种差异表达最为显著的miRNAs，且这些miRNAs在自身免疫性疾病中均存在明显的表达失调。针对SLE的最具说服力的结果为：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RA的显著结果为血液样本中的miR-21、miR-24、miR-26a、miR-155及miR-223；针对T1D的显著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。值得关注的是，部分miRNAs可在多种自身免疫性疾病中呈现差异表达，例如miR-21、miR-26a、miR-155、miR-148a、miR-223。这些miRNAs通常与免疫应答相关，且在皮肤、关节、肺脏及肾脏等特定器官中，与免疫系统活化及炎症反应增强密切相关。上述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，同时也可作为潜在的治疗靶点。