Ayeldeen Ghada, Badr Bahaa Mohammed, Awaji Aeshah A, Gaber Dalia A, Elelwany Doaa Abdellatif, Al Abdulqader Abdulrhman Khaled, Shaker Olfat G, Abd-Elmawla Mai A
Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Giza 12613, Egypt.
Department of Basic and Clinical Medical Sciences, Faculty of Dentistry, Zarqa University, Zarqa 132222, Jordan.
ACS Chem Neurosci. 2025 Jul 2;16(13):2513-2527. doi: 10.1021/acschemneuro.5c00299. Epub 2025 Jun 16.
Multiple sclerosis (MS) is an autoimmune disease associated with neurological impairments. The study aimed to evaluate the role of the noncoding RNAs THRIL/miR-137 in MS pathogenesis via studying their effect on the immunological transcriptional loop STAT4/STAT6/GATA3, and their association with MS-related neurological impairments and disease subtypes. Overall, 148 participants were included: 74 MS patients and 74 matched healthy controls. Gene expressions of THRIL, miR-137, STAT4, STAT6, and GATA3 were assessed using reverse transcription quantitative polymerase chain reaction (RT-qPCR). The potential protein interaction networks of these genes were predicted using bioinformatic analysis. Compared with the control group, THRIL, STAT4, and GATA3 were upregulated, whereas miR-137 and STAT6 were downregulated in MS patients. Furthermore, THRIL, STAT4, and GATA3 were upregulated, while miR-137 and STAT6 were downregulated in MS patients with Expanded Disability Status Scale (EDSS) ≥ 3.5, relative to patients with EDSS < 3.5. Similarly, THRIL, STAT4, and GATA3 were upregulated, while miR-137 and STAT6 were downregulated in Secondary Progressive MS (SPMS) patients relative to Relapsing-Remitting MS (RRMS). Notably, receiver operating characteristic (ROC) curve analysis revealed that THRIL, miR-137, and STAT4/STAT6/GATA3 can be used in differentiating between MS patients with neurological impairments as well as MS subtypes. Significantly, logistic analysis revealed that THRIL, miR-137, and STAT4/STAT6/GATA3 could act as predictors to diagnose MS and the associated neurological impairments. In conclusion, the study demonstrated for the first time the role of THRIL/miR-137 in regulating the immunological transcriptional loop STAT4/STAT6/GATA3, which may contribute to neurological complications. These findings provide insights into MS pathogenesis and highlight the potential of these genes as biomarkers or therapeutic targets.
多发性硬化症（MS）是一种与神经功能障碍相关的自身免疫性疾病。该研究旨在通过研究非编码RNA THRIL/miR-137对免疫转录环STAT4/STAT6/GATA3的影响及其与MS相关神经功能障碍和疾病亚型的关联，来评估它们在MS发病机制中的作用。总体而言，共纳入148名参与者：74例MS患者和74名匹配的健康对照。采用逆转录定量聚合酶链反应（RT-qPCR）评估THRIL、miR-137、STAT4、STAT6和GATA3的基因表达。使用生物信息学分析预测这些基因的潜在蛋白质相互作用网络。与对照组相比，MS患者中THRIL、STAT4和GATA3上调，而miR-137和STAT6下调。此外，与扩展残疾状态量表（EDSS）<3.5的患者相比，EDSS≥3.5的MS患者中THRIL、STAT4和GATA3上调，而miR-137和STAT6下调。同样，与复发缓解型MS（RRMS）患者相比，继发进展型MS（SPMS）患者中THRIL、STAT4和GATA3上调，而miR-137和STAT6下调。值得注意的是，受试者工作特征（ROC）曲线分析显示，THRIL、miR-137和STAT4/STAT6/GATA3可用于区分有神经功能障碍的MS患者以及MS亚型。重要的是，逻辑分析显示，THRIL、miR-137和STAT4/STAT6/GATA3可作为诊断MS及相关神经功能障碍的预测指标。总之，该研究首次证明了THRIL/miR-137在调节免疫转录环STAT4/STAT6/GATA3中的作用，这可能导致神经并发症。这些发现为MS发病机制提供了见解，并突出了这些基因作为生物标志物或治疗靶点的潜力。
