Circulating MicroRNA Profiling in Human Health

Circulating microRNAs are small non-coding RNAs detectable in body fluids that serve as stable indicators of physiological and pathological states. Profiling these molecules has transformed understanding of disease mechanisms and enabled development of non-invasive diagnostic and prognostic strategies. Advances in sequencing methods, quantitative PCR, digital PCR and emerging single-molecule detection platforms have improved sensitivity and specificity for miRNA measurement. Studies have demonstrated that circulating miRNAs reflect tissue-specific expression patterns, are packaged within extracellular vesicles or bound to proteins, and can be reliably quantified despite pre-analytical variables such as sample type, storage and haemolysis. Comprehensive profiling has uncovered miRNA signatures associated with cancer, cardiovascular disease, pregnancy and metabolic disorders, paving the way for early detection, monitoring of treatment response and personalised medicine. Standardisation of collection and processing protocols, together with robust normalisation strategies, underpins the clinical translation of circulating miRNA biomarkers.

Research from Nature Portfolio

Recent studies have expanded the repertoire of circulating small RNAs by revealing a predominance of molecules terminating in cyclic phosphate groups and uncovering distinct sequence profiles for these species. A novel sequencing approach, capable of capturing both cyclic-phosphate and hydroxyl-terminated RNAs, has identified thousands of previously uncharacterised small RNAs in plasma and demonstrated their association with key biogenesis enzymes and Argonaute-2 complexes, indicating functional roles in gene regulation and apoptosis. Foundational transcriptome analyses of large cohorts have systematically catalogued diverse extracellular RNAs—including microRNAs, piwi-interacting RNAs and small nucleolar RNAs—in human plasma, establishing a robust reference atlas and demonstrating consistent detection across populations. These efforts have collectively broadened the landscape of circulating RNA biomarkers and provided valuable tools for future biomarker discovery and mechanistic studies.

Circulating MicroRNA Profiling in Human Health publication trend

The graph below shows the total number of articles in circulating microrna profiling in human health across all publications each year (not limited to Nature Index journals).

Technical terms

microRNA (miRNA): Small non-coding RNA of approximately 19–25 nucleotides that modulates gene expression post-transcriptionally by base-pairing with target mRNAs.

Liquid biopsy: Minimally invasive sampling of body fluids to obtain molecular biomarkers such as circulating nucleic acids and extracellular vesicles.

Biomarker: A biological characteristic that is objectively measured and evaluated as an indicator of normal or pathogenic processes or responses to therapy.

TANT-seq: A sequencing method designed to capture small RNAs bearing 2′,3′-cyclic phosphate termini alongside those with hydroxyl ends, enabling comprehensive profiling.

Single-molecule detection: Analytical approaches that allow the direct measurement of individual RNA molecules without amplification for enhanced sensitivity and quantification accuracy.

References

1. Profiling small RNAs in fecal immunochemical tests: is it possible?. Molecular Cancer (2023).
2. Discovery of the major 15–30 nt mammalian small RNAs, their biogenesis and function. Nature Communications (2023).
3. Machine-Learning-Based Single-Molecule Quantification of Circulating MicroRNA Mixtures. ACS Sensors (2023).
4. Diverse human extracellular RNAs are widely detected in human plasma. Nature Communications (2016).
5. Stability of Circulating Blood-Based MicroRNAs – Pre-Analytic Methodological Considerations. PLOS ONE (2017).
6. Haemolysis during Sample Preparation Alters microRNA Content of Plasma. PLOS ONE (2011).
7. Plasma Processing Conditions Substantially Influence Circulating microRNA Biomarker Levels. PLOS ONE (2013).