Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran.
Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Sci Rep. 2022 Nov 7;12(1):18932. doi: 10.1038/s41598-022-23723-7.
Systemic sclerosis (SSc) or scleroderma is a multiorgan rheumatoid disease characterized by skin tightening or organ dysfunction due to fibrosis, vascular damage, and autoimmunity. No specific cause has been discovered for this illness, and hence no effective treatment exists for it. On the other hand, due to the lack of diagnostic biomarkers capable of effectively and specifically differentiating the patients, early diagnosis has not been possible. Due to their potent regulatory roles in molecular pathways, microRNAs are among the novel candidates for the diagnosis and treatment of diseases like SSc. MiR-27a is a microRNA known for its role in the pathogenesis of fibrosis and cancer, both of which employ similar signaling pathways; hence we hypothesized that Mir-27a could be dysregulated in the blood of individuals affected by SSc and it might be useful in the diagnosis or treatment of this disease. Blood was collected from 60 SSc patients (30 limited and 30 diffuse) diagnosed by a rheumatologist according to ACR/AULAR criteria; following RNA isolation and cDNA synthesis; real-time qPCR was performed on the samples using Taq-Man probes and data were analyzed by the ΔΔCT method. Also, potential targets of miR-27a were evaluated using bioinformatics. It was revealed that miR-27a was significantly down-regulated in SSc patients in comparison to healthy individuals, but there was no difference in miR-27 expression between limited and diffused SSc patients. Besides, miR-27a was found to target several contributing factors to SSc. It seems that miR-27a has a protective role in SSc, and its downregulation could result in the disease's onset. Based on bioinformatics analyses, it is speculated that miR-27a likely targets factors contributing to the pathogenesis of SSc, which are elevated upon the downregulation of miR-27a; hence, miR-27a mimics could be considered as potential therapeutic agents for the treatment of SSc in future studies. Since no difference was observed between limited and diffuse patient groups, it is unlikely that this microRNA has a role in disease progression. According to ROC analysis of qPCR data, miR-27a could be employed as a valuable diagnostic biomarker for SSc.
系统性硬化症(SSc)或硬皮病是一种多器官类风湿疾病,其特征是纤维化、血管损伤和自身免疫导致皮肤紧绷或器官功能障碍。目前尚未发现这种疾病的特定原因,因此也没有有效的治疗方法。另一方面,由于缺乏能够有效且特异性区分患者的诊断生物标志物,因此无法进行早期诊断。由于 microRNA 在分子途径中具有强大的调节作用,因此它们是用于诊断 SSc 等疾病的新型候选物之一。miR-27a 是一种已知在纤维化和癌症发病机制中起作用的 microRNA,这两种疾病都采用相似的信号通路;因此,我们假设 Mir-27a 可能在受 SSc 影响的个体的血液中失调,并且它可能对这种疾病的诊断或治疗有用。从 60 名根据 ACR/AULAR 标准由风湿病学家诊断的 SSc 患者(30 名局限性和 30 名弥漫性)中采集血液;在 RNA 分离和 cDNA 合成后;使用 Taq-Man 探针对样品进行实时 qPCR,并通过 ΔΔCT 方法分析数据。此外,还使用生物信息学评估了 miR-27a 的潜在靶标。结果表明,与健康个体相比,miR-27a 在 SSc 患者中显著下调,但局限性和弥漫性 SSc 患者之间的 miR-27 表达没有差异。此外,发现 miR-27a 靶向 SSc 的几个致病因素。miR-27a 在 SSc 中似乎具有保护作用,其下调可能导致疾病的发生。基于生物信息学分析,推测 miR-27a 可能靶向导致 SSc 发病机制的因素,这些因素在 miR-27a 下调时升高;因此,miR-27a 模拟物可能被视为未来治疗 SSc 的潜在治疗剂。由于在局限性和弥漫性患者组之间未观察到差异,因此该 microRNA 不太可能在疾病进展中发挥作用。根据 qPCR 数据的 ROC 分析,miR-27a 可作为 SSc 的有价值的诊断生物标志物。