Altered miR-203a and miR-3622b-5p expressions in multiple sclerosis: novel correlations with apoptotic gene...

Defective apoptosis of autoreactive immune cells contributes to multiple sclerosis (MS) pathogenesis. Survivin (BIRC5), an anti-apoptotic protein, and interleukin-4 (IL-4), а cytokine with dual immunomodulatory roles, are potential key players. This study investigates the expression of BIRC5, IL-4, and three apoptosis-associated miRNAs (miR-203a, miR-3622b-5p, miR-198) in MS, focusing on their regulatory interplay.

Whole blood RNA from 28 relapsing-remitting MS patients and 27 healthy controls was analyzed via qRT-PCR. BIRC5 and IL-4 expression were significantly elevated in MS patients (p = 0.008; p = 0.012). miR-203a (p = 0.005) and miR-3622b-5p (p = 0.003) showed marked upregulation, while miR-198 remained unchanged. Bioinformatics prediction (TargetScan/ miRDB) identified conserved binding sites for miR-203a and miR-3622b-5p in the 3'UTR of BIRC5 and IL-4, supported by strong correlations (BIRC5-miR-203a: r = 0.65, p = 0.002; IL-4-miR-3622b-5p: r = 0.58, p = 0.007). Gene ontology analysis linked these molecules to apoptotic resistance (GO:0043066) and Th2 signaling (KEGG:04630).

This study reveals a dysregulated BIRC5/IL-4/miRNA axis in MS, where miR-203a and miR-3622b-5p potentially enhance survivin and IL-4 expression, promoting immune cell survival. These findings highlight miRNA-mediated post-transcriptional regulation as a novel therapeutic target for restoring apoptotic balance in MS.