Investigation of miR-335-5p and Its Target Gene C1QA Associated with the Complement System in Conversion from Clinically Isolated Syndrome to Multiple Sclerosis

Abstract

Introduction: Multiple sclerosis (MS), an autoimmune disease, attacks the central nervous system, causing inflammation and damage. Diagnosed in four forms, many clinically isolated syndrome (CIS) patients progress to relapsing-remitting MS (RRMS). C1QA, a molecule linked to MS, might be a treatment target due to its abnormal activity in the disease. This study investigated mir-335-5p and its targeting C1QA expression as potential biomarkers for disease progression. This relationship was also evaluated from an epigenetic perspective between CIS, RRMS and control groups. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from 18 CIS, 32 RRMS, and 16 control blood samples. RNA isolation and Quantitative Real-Time PCR (qRT-PCR) were performed to detect the expression levels of C1QA and miR-335-5p, while C1QA protein levels were determined using ELISA. Results: The data revealed significant increases in both C1QA gene expression (p=0.0291) and miR-335-5p expression (p=0.0196) in CIS patients compared to controls. Although increased expression levels were observed for both parameters in RRMS patients versus controls, they did not reach statistical significance. Patients with RRMS showed lower levels of C1QA and miR-335-5p compared to those with CIS. Notably, the decrease in miR-335-5p was statistically significant (p=0.0442). No significant difference in C1QA protein levels was observed among the groups (p >0.05). Conclusion: miR-335-5p and C1QA emerge as potential biomarkers for MS progression, exhibiting significant upregulation in CIS compared to controls. miR-335-5p also shows significant downregulation in RRMS compared to CIS. These findings support the potential of miR-335-5p for distinguishing and understanding the progression of both CIS and RRMS