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MicroRNAs (miRNAs) have emerged as key regulators in the pathogenesis of amyotrophic lateral sclerosis (ALS). Despite growing evidence that miRNAs exhibit altered expression profiles in ALS, their utility as a biomarker remains limited. To address this, we conducted a meta-analysis using the Robust Rank Aggregation package, incorporating 20 differential miRNA profiling studies. Among these, miR-146a-5p emerged as the most dysregulated and significant miRNA in ALS (P = 0.0000142, P-adj = 0.0096), particularly in extracellular vesicle-derived studies. To evaluate its diagnostic accuracy, we validated miR-146a-5p expression in serum-derived exosomes and observed a significant increase in sporadic ALS (sALS) patients (n = 22) as compared to healthy controls (n = 18). Moreover, higher levels of miR-146a-5p were strongly associated with longer survival (≥ 5 years) (P = 0.0135), with a positive correlation between miR-146a-5p expression and survival duration (P = 0.0313) in sALS patients. Further, gene set enrichment analysis of miR-146a-5p target genes highlighted critical involvement of the Immune system and NF-kappa B signaling pathways in ALS pathophysiology. These findings highlight miR-146a-5p as a potential biomarker for ALS.
Rawat et al. (Tue,) studied this question.