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Published on: June 15, 2018
Differential expression of microRNA in serum fractions and association of Argonaute 1 microRNAs with heart failure
Eti Meiri1, Natalia Volinsky2,3, Nir Dromi1
1Rosetta Genomics Ltd, Rehovot, Israel.
Abstract:
The serum or plasma microRNA (miRNA) molecules have been suggested as diagnostic and prognostic biomarkers, in various pathological conditions. However, these molecules are also found in different serum fractions, such as exosomes and Argonaute (Ago) protein complexes. Ago1 is the predominant Ago protein expressed in heart tissue. The objective of the study was to examine the hypothesis that Ago1-associated miRNAs may be more relevant to cardiac disease and heart failure compared with the serum. In total, 84 miRNA molecules were screened for their expression in the whole serum, exosomes and Ago1, and Ago2 complexes. Ago1-bound miR-222-3p, miR-497-5p and miR-21-5p were significantly higher, and let-7a-5p was significantly lower in HF patients compared with healthy controls, whereas no such difference was observed for those markers in the serum samples among the groups. A combination of these 4 miRNAs into an Ago1-HF score provided a ROC curve with an AUC of 1, demonstrating clear discrimination between heart failure patients and healthy individuals. Ago1 fraction might be a better and more specific platform for identifying HF-related miRNAs compared with the whole serum.
Insights
Argonaute protein 1 (Ago1)-associated microRNAs (miRNAs) show greater relevance for diagnosing heart failure (HF) than serum miRNAs. A specific panel of Ago1-bound miRNAs accurately distinguishes HF patients from healthy individuals.
Area of Science:
- Biochemistry
- Molecular Biology
- Cardiology
Background:
- Serum microRNAs (miRNAs) are explored as biomarkers for various diseases.
- miRNAs exist in serum fractions like exosomes and Argonaute (Ago) protein complexes.
- Ago1 is the primary Ago protein in cardiac tissue.
Purpose of the Study:
- To investigate if Ago1-associated miRNAs are more indicative of cardiac disease and heart failure (HF) than serum miRNAs.
- To identify specific miRNAs bound to Ago1 that correlate with HF.
Main Methods:
- Screened 84 miRNA molecules for expression in whole serum, exosomes, and Ago1/Ago2 complexes.
- Compared miRNA expression levels between HF patients and healthy controls.
- Developed an Ago1-HF score using specific miRNAs.
Main Results:
- Ago1-bound miR-222-3p, miR-497-5p, and miR-21-5p were elevated; let-7a-5p was decreased in HF patients compared to controls.
- No significant differences were found in the whole serum samples for these miRNAs.
- The Ago1-HF score achieved an Area Under the Curve (AUC) of 1, indicating perfect discrimination between HF patients and controls.
Conclusions:
- Ago1-associated miRNAs offer a more specific platform for identifying HF biomarkers compared to whole serum.
- A panel of four specific miRNAs bound to Ago1 can effectively diagnose heart failure.
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