28/12/2025
Circulating microRNAs
Circulating microRNAs (miRNAs) are short, noncoding RNA molecules released into the bloodstream in stable forms — bound to proteins (e.g., Argonaute), associated with lipoproteins, or enclosed within extracellular vesicles. Because they remain detectable in plasma and serum, circulating miRNAs are attractive, minimally invasive biomarker candidates across oncology, cardiology, infectious diseases and neurology.
Why laboratories should pay attention:
• Stability and accessibility. Many circulating miRNAs resist RNase degradation in blood and can be measured from routine clinical specimens, enabling liquid-biopsy workflows.
• Broad clinical signal. Distinct circulating-miRNA signatures have been reported for diagnosis, prognosis and treatment response across multiple disease areas.
• Biological relevance. miRNA profiles often reflect underlying pathophysiology (cell type of origin, injury, inflammation or tumor-related processes), offering mechanistic insight in addition to diagnostic signal.
Critical caveats:
• Pre-analytical variability is large. Serum versus plasma choice, collection tube, time to centrifugation, degree of hemolysis, and storage/freeze–thaw history substantially affect measured miRNA levels. Lock and document SOPs.
• Platform and normalization matter. qRT-PCR, small RNA sequencing and hybridization platforms can yield different profiles. Spike-in controls and normalization strategies mitigate but do not eliminate inter-method variability. Validate platform performance for your intended use.
• Reproducibility is required for clinical uptake. Many candidate miRNA biomarkers originate from single-center studies. Multi-site validation, standardized workflows, and clear clinical decision pathways are necessary before routine deployment.
Practical roadmap for implementation:
Define the clinical question (diagnosis, prognosis, therapy monitoring) and choose the specimen type accordingly.
Lock pre-analytical SOPs (tube type, processing time, centrifugation, storage) and document every sample.
Select and validate a platform for the intended use; perform method comparisons and assess intra/inter-assay precision.
Run a pilot study with a well-annotated cohort, then pursue multi-center validation before offering clinical reports.
Summary:
Circulating miRNAs are biologically informative and translationally promising biomarkers. Their clinical value depends on rigorous pre-analytics, validated analytical workflows, and reproducible multi-site evidence.