Chonnam Med J.  2015 Aug;51(2):51-57. 10.4068/cmj.2015.51.2.51.

Extracellular microRNAs as Biomarkers in Human Disease

• Kim YK

• KMID: 2172132
• DOI: http://doi.org/10.4068/cmj.2015.51.2.51

Abstract

Dysregulation of microRNA (miRNA) levels is observed in diverse disease states. Early studies showed that by analyzing the expression profile of miRNAs in the tissue sample of a diseased person, it was possible to classify the disease into a specific subtype. To be used for diagnostic purposes more practically, however, a less invasive method than tissue biopsy is required. Surprisingly, it was discovered that a notable amount of extracellular miRNAs circulate throughout the body fluids with high stability. Moreover, the expression profile of miRNAs was shown to differ considerably between healthy and diseased people. In addition, evidence has been accumulating of extracellular miRNAs acting as signaling molecules between distantly located cells. If the expression profile faithfully reflects the disease states, the profiling of extracellular miRNAs will become a useful means of early warning or diagnosis of diverse diseases, replacing more invasive biopsy methods.

Keyword

MicroRNAs; Biological markers; Body fluids

MeSH Terms

Biomarkers*
Biopsy
Body Fluids
Diagnosis
Humans*
MicroRNAs*
MicroRNAs

Figure

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  FIG. 1 Timeline of the important discoveries about the use of miRNAs as biomarkers. See text for details.

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  FIG. 2 Numbers of papers published each year about miRNA, miRNA biomarkers, and extracellular miRNA biomarkers, respectively. Only research papers were counted in PubMed. To count the papers about miRNA (solid line), papers containing the term "microRNA" or "microRNAs" in the title or abstract were searched. For papers about miRNA as a biomarker (gray bar), papers containing the term "biomarker" or "biomarkers" in the title or abstract were counted among the miRNA papers. For the papers about miRNA as an extracellular biomarker (black bar), papers were counted that additionally contained the term "blood-based", "extracellular", "exosome", "exosomes", "plasma", or "serum" among the papers about miRNA biomarkers.

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  FIG. 3 Origin and distribution of extracellular miRNAs. (A) Release of miRNAs into the extracellular space. After the production of mature miRNAs, some portion of miRNAs might be incorporated into the multivesicular body and released into the extracellular space through exosomes. Another portion of miRNAs might be released directly through budding vesicles. (B) Circulating miRNAs in the blood vessels. The miRNAs, incorporated in the proteins such as Ago2, could circulate through the blood. It was also found that miRNAs exist in the extracellular vesicle, the exosome, and high-density lipoprotein (HDL). (C) miRNA-containing body fluids. Most of the body fluids were found to contain miRNAs.

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