Unraveling the Role of THRIL/miR-137 in Fine-Tuning the Immunological Transcriptional Loop STAT4/STAT6/GATA3 in Multiple Sclerosis: Implications on Neurological Complications and Disease Subtypes.

Abstract

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.