Mosarrezaii Aghdam Arash, Rezaei Somaye, Zarza Nalivan Fariba, Babaie Farhad, Amiri Nikpour Mohammad Reza, Torkamandi Shahram
Neurophysiology Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran.
Department of Neurology, Imam Khomeini Hospital, Urmia University of Medical Sciences, Urmia, Iran.
Immunol Invest. 2022 Jul;51(5):1149-1161. doi: 10.1080/08820139.2021.1909616. Epub 2021 Apr 19.
Multiple sclerosis (MS) is a chronic neuroinflammatory disease of the brain and spinal cord. Evidences have demonstrated that microRNAs (miRNAs) are involved in the pathological process of MS that may confer a valuable diagnostic biomarker for disease diagnosis, prognosis, and treatment. Hence, we assessed the expression pattern of miR-125a-5p and miR-218-5p in the peripheral blood mononuclear cells (PBMCs) of subjects with relapsing-remitting multiple sclerosis (RRMS). We recruited 50 RRMS patients and 50 age- and sex-matched healthy control subjects. PBMCs were isolated from the peripheral blood samples, RNA content was extracted, cDNA was synthesized, and finally expression level of miRNAs was determined using quantitative real-time PCR. Our data indicate significant downregulation of both miR-125a-5p and miR-218-5p in RRMS patients compared to healthy controls (< .0001). The levels of both miRNAs were significantly downregulated in an age-dependent manner compared with consistent healthy control groups (30-40 years old < .0001). Expression level of miR-218-5p was significantly changed in only female patients (Female group < .0001; Male group = .12). Receiver operating characteristic (ROC) curve data indicated that the expression levels of both miRNAs were able to discriminate RRMS patients from healthy subjects (< .05). Moreover, bioinformatic enrichment analysis revealed that the target genes of these miRNAs had cardinal roles in the regulation of key biological pathways involved in the clinical course and pathogenesis of MS. Collectively, our results suggested that miR-125a-5p and miR-218-5p play a role in RRMS pathogenesis and have an age- and sex-dependent expression pattern in these patients.
多发性硬化症(MS)是一种发生于脑和脊髓的慢性神经炎症性疾病。有证据表明,微小RNA(miRNA)参与了MS的病理过程,这可能为疾病的诊断、预后和治疗提供有价值的诊断生物标志物。因此,我们评估了复发缓解型多发性硬化症(RRMS)患者外周血单个核细胞(PBMC)中miR-125a-5p和miR-218-5p的表达模式。我们招募了50例RRMS患者和50例年龄及性别匹配的健康对照者。从外周血样本中分离出PBMC,提取RNA含量,合成cDNA,最后使用定量实时PCR测定miRNA的表达水平。我们的数据表明,与健康对照相比,RRMS患者中miR-125a-5p和miR-218-5p均显著下调(<0.0001)。与一致的健康对照组(30-40岁<0.0001)相比,这两种miRNA的水平均以年龄依赖的方式显著下调。仅在女性患者中,miR-218-5p的表达水平有显著变化(女性组<0.0001;男性组=0.12)。受试者工作特征(ROC)曲线数据表明,这两种miRNA的表达水平能够区分RRMS患者和健康受试者(<0.05)。此外,生物信息学富集分析显示,这些miRNA的靶基因在调节MS临床病程和发病机制所涉及的关键生物学途径中起主要作用。总体而言,我们的结果表明,miR-125a-5p和miR-218-5p在RRMS发病机制中起作用,并且在这些患者中具有年龄和性别依赖性的表达模式。