The majority of microRNAs detectable in serum and saliva is concentrated in exosomes
Open accessAbstract
There is an increasing interest in using microRNAs (miRNA) as biomarkers in autoimmune diseases. They are easily accessible in many body fluids but it is controversial if they are circulating freely or are encapsulated in microvesicles, particularly exosomes. We investigated if the majority of miRNas in serum and saliva are free-circulating or concentrated in exosomes. Exosomes were isolated by ultracentrifugation from fresh and frozen human serum and saliva. The amount of selected miRNAs extracted from the exosomal pellet and the exosome-depleted serum and saliva was compared by quantitative RT-PCR. Some miRNAs tested are ubiquitously expressed, others were previously reported as biomarkers. We included miRNAs previously reported to be free circulating and some thought to be exosome specific. The purity of exosome fraction was confirmed by electronmicroscopy and western blot. The concentration of miRNAs was consistently higher in the exosome pellet compared to the exosome-depleted supernatant. We obtained the same results using an equal volume or equal amount of total RNA as input of the RT-qPCR. The concentration of miRNA in whole, unfractionated serum, was between the exosomal pellet and the exosome-depleted supernatant. Selected miRNAs, which were detectable in exosomes, were undetectable in whole serum and the exosome-depleted supernantant. Exosome isolation improves the sensitivity of miRNA amplification from human biologic fluids. Exosomal miRNA should be the starting point for early biomarker studies to reduce the probability of false negative results involving low abundance miRNAs that may be missed by using unfractionated serum or saliva.
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miRNAs can be secreted into extracellular fluids and transported to target cells via vesicles such as exosomes or by binding to proteins including Argonautes.
“miRNAs can be secreted into extracellular fluids and transported to target cells via vesicles, such as exosomes, or by binding to proteins, including Argonautes.”
From Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation (2018) · cites this paper as [120]
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- Authors
- Gallo, A., Tandon, M., Alevizos, I., & Illei, G. G.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Illei, Gabor G.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-03-09
- Volume
- 7
- Issue
- 3
- Pages
- e30679
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3302865
- OpenAlex
- W2141138739
- Cited by
- 1,060
- References
- 14
- Citations by year
- 2026: 27 · 2025: 38 · 2024: 63 · 2023: 69 · 2022: 81 · 2021: 113 · 2020: 105 · 2019: 71 · 2018: 77 · 2017: 86 · 2016: 84 · 2015: 85 · 2014: 67 · 2013: 70 · 2012: 24
- FWCI
- 31.65
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, public-domain)
- PubMed Central (publishedVersion, public-domain)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health
- National Institute of Dental and Craniofacial Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- microRNA, exosomes, serum, saliva, exosome isolation, circulating microRNAs, biomarkers, autoimmune disease, liquid biopsy
- MeSH terms
- Humans, Microscopy, Electron, Saliva, Blotting, Western, Biomarkers, Reverse Transcriptase Polymerase Chain Reaction, MicroRNAs, Exosomes
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