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.

miRNAs as Biomarkers and Therapeutic Targets in Non-Small Cell Lung Cancer: Current Perspectives

“…In a study by Weber et al [64], the total amount of RNA isolated from various body fluids was found to range widely from 113 to 48,240 μg/L. Plasma, cerebrospinal fluid, pleural effusion fluid and urine contained less RNA than seminal fluid, saliva and bronchoalveolar lavage fluid did.…”

“…The absolute total amount of extracellular RNA in plasma was estimated to be in the low nanomolar range. The concentration of extracellular miRNA in the plasma of healthy donors was estimated to be approximately 100 fM [64,65]. The concentrations of individual miRNAs are therefore thought to be a fraction of this value.…”

Circulating microRNAs and hypertension—from new insights into blood pressure regulation to biomarkers of cardiovascular risk

“…[7,8] They have subsequently been detected in a wide range of bio-fluids, including urine, saliva and cerebrospinal fluid. [9] These circulating microRNAs have a number of characteristics that make them attractive targets for biomedical research -they are remarkably stable in the blood, appear in concentrations measurable by current techniques and often show tissue specific expression; furthermore, they are likely to become dysregulated prior to physical symptoms of disease becoming present. [10] These factors, paired with limited availability and difficulty in obtaining human tissue samples, have meant that circulating microRNAs studies (rather than tissue microRNAs) have predominated in the search for microRNA-based biomarkers in hypertension.…”

Cell‐to‐cell communication: microRNAs as hormones

“…EVs participate in cell–cell communication and can typically be classified based on their size (from 4 to 10 microns), intracellular origin, and density (Cocucci and Meldolesi, 2011; Raposo and Stoorvogel, 2013; Valadi et al ., 2007). EVs can be found in all different body fluids, such as blood, serum, plasma, saliva, urine, and pleural effusions (Fernandez‐Mercado et al ., 2015; Liu et al ., 2017a; Mitchell et al ., 2008; Ortiz‐Quintero, 2016; Weber et al ., 2010). In the last decade, several studies have shown that EVs are enriched for various proteins, such as cytokines, messenger RNAs, lipids, and noncoding RNAs, such as miRNAs and long noncoding RNAs (lncRNAs) (Colombo et al ., 2013; Valadi et al ., 2007).…”