Insights from meta-analysis and experimental validation identify exosomal miR-146a-5p as a potential biomarker for

Anjali Rawat1, Shiffali Khurana1,2, Sagar Verma1,3,4

  • 1Department of Biotechnology and Research, Sir Ganga Ram Hospital, Delhi, 110060, India.

Scientific Reports
|October 1, 2025
PubMed

Insights

MicroRNAs (miRNAs) are key in amyotrophic lateral sclerosis (ALS). This study identifies miR-146a-5p as a significant biomarker in ALS patients, showing altered levels and association with longer survival.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biomarker Discovery

Background:

  • MicroRNAs (miRNAs) play a crucial role in the pathogenesis of amyotrophic lateral sclerosis (ALS).
  • Altered miRNA expression is observed in ALS, but their diagnostic utility is limited.
  • Identifying reliable miRNA biomarkers is essential for ALS diagnosis and prognosis.

Purpose of the Study:

  • To identify significant miRNAs associated with ALS through meta-analysis.
  • To evaluate the diagnostic accuracy of candidate miRNAs, specifically miR-146a-5p.
  • To explore the correlation between miR-146a-5p levels, survival, and underlying biological pathways in ALS.

Main Methods:

  • A meta-analysis of 20 differential miRNA profiling studies was performed using Robust Rank Aggregation.
  • miR-146a-5p expression was validated in serum-derived exosomes from sporadic ALS (sALS) patients and healthy controls.
  • Gene set enrichment analysis was conducted on miR-146a-5p target genes.

Main Results:

  • miR-146a-5p was identified as the most significantly dysregulated miRNA in ALS.
  • Elevated miR-146a-5p levels were observed in sALS patients compared to controls.
  • Higher miR-146a-5p expression correlated with longer survival in sALS patients.
  • Immune system and NF-kappa B signaling pathways were implicated through miR-146a-5p target analysis.

Conclusions:

  • miR-146a-5p is a promising and significant biomarker for amyotrophic lateral sclerosis (ALS).
  • Its expression levels are associated with disease status and patient survival.
  • miR-146a-5p may play a role in ALS pathophysiology via immune and NF-kappa B signaling.

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