The microRNA spectrum in 12 body fluids

Abstract

Background: MicroRNAs (miRNAs) are small, noncoding RNAs that play an important role in regulating various biological processes through their interaction with cellular messenger RNAs. Extracellular miRNAs in serum, plasma, saliva, and urine have recently been shown to be associated with various pathological conditions including cancer.

Methods: With the goal of assessing the distribution of miRNAs and demonstrating the potential use of miRNAs as biomarkers, we examined the presence of miRNAs in 12 human body fluids and urine samples from women in different stages of pregnancy or patients with different urothelial cancers. Using quantitative PCR, we conducted a global survey of the miRNA distribution in these fluids.

Results: miRNAs were present in all fluids tested and showed distinct compositions in different fluid types. Several of the highly abundant miRNAs in these fluids were common among multiple fluid types, and some of the miRNAs were enriched in specific fluids. We also observed distinct miRNA patterns in the urine samples obtained from individuals with different physiopathological conditions.

Conclusions: MicroRNAs are ubiquitous in all the body fluid types tested. Fluid type-specific miRNAs may have functional roles associated with the surrounding tissues. In addition, the changes in miRNA spectra observed in the urine samples from patients with different urothelial conditions demonstrates the potential for using concentrations of specific miRNAs in body fluids as biomarkers for detecting and monitoring various physiopathological conditions.

Fig. 1. The body fluid types can be grouped into 2 major clusters based on the profile of commonly expressed miRNAs (unsupervised hierarchical clustering)

Plasma is separate from the 2 major clusters.

Fig. 2. miRNA distribution in various urine samples

(A), Examples of miRNAs detectable only in urine samples other than the control samples. (B), miRNAs that show differences between the urothelial cancers. ΔCt, difference in cycle threshold values.

Fig. 3. Mean concentration of miR-302c across different fluid types

The concentrations were averaged among all samples from the same fluid type. Amniotic fluid shows a higher concentration than the other body fluid types.