Exosomes are 50–90 nm membrane-derived vesicles found in bodily fluids including blood, saliva, and urine. They encapsulate proteins and mRNA as well as miRNA that may be exchanged as a signaling mechanism between cells. Encapsulated mRNA and miRNA are relatively stable because exosomes protect nucleic acids from extracellular degradation.

Circulating miRNAs are potential biomarkers of various pathological conditions¹ and have been characterized previously in total urine specimens and exosomes from body fluids other than urine², but have yet to be studied in urinary exosomes. Advances have been made in understanding the role of miRNAs in cancer pathogenesis, but less is known about their role in other chronic diseases. Studies have been reported associating certain miRNAs with hypertension but miRNAs have not yet been directly linked to sodium metabolism.

To characterize the urinary exosome miRNome, researchers at the University of Virginia Health System used LC Sciences microarrays to explore the miRNA spectrum present within urinary exosomes from ten individuals that had completed a salt sensitivity clinical study³. Groups exhibiting extremes of salt sensitivity of blood pressure were compared to a group of normal individuals who had blood pressure that did not change dependent on sodium consumption, i.e. they were salt-resistant. In the microarray, potential biomarkers were sought based on these three phenotypes defined below.

Of the 194 miRNAs detected, 45 were significantly different between the SS and SR individuals or between the ISS and SR subjects. A search of the literature for each of the 45 miRNAs that were significantly different between SS or ISS vs. SR individuals, revealed that only 21 were previously cited as extracellular secreted miRNAs in serum or other bodily fluids (http://atlas.dmi.unict.it/mirandola/index.html). The 24 miRNAs that have not been described as secreted from cells or found in body fluids can be considered unique to urinary exosomes and strongly indicate that serum exosomal miRNAs do not pass into the urine in appreciable quantities.

Investigating renal cellular pathophysiology through the study of intracellular biomarkers has the potential of providing a deeper understanding of how individuals express unique patterns of salt sensitivity of blood pressure. Ultimately, personalized therapeutic approaches to controlling salt-related illnesses will result from these new diagnostic techniques.

To identify the miRNA signatures specific for pancreatic cancer (PCa), researchers from Brock University, Canada utilized LC Sciences miRNA expression profiling service for urine samples from 8 PCa patients, 12 BPH patients and 10 healthy males⁴. Differential expression of two individual miRNAs between healthy males and BPH patients was detected and found to possibly target genes related to PCa development and progression.  The proposed PCa miRNA signatures may therefore be of great value for the accurate diagnosis of PCa and BPH. This exploratory study identified several possible targets that merit further investigation towards the development and validation of diagnostically useful, non-invasive, urine-based tests that might not only help diagnose PCa but also possibly help differentiate it from BPH.

More recently, researchers from the University of Rochester purified exosomes from bladder cancers, immortalized bladder cells, and urine of healthy volunteers and muscle invasive bladder cancer patients⁵. The researchers  performed miRNA expression profiling microarray (LC Sciences). The results showed significant difference miRNAs between cancer cells vs normal cells. Some of cancer-specific miRNAs which have shown to play critical roles in tumorigenesis and cancer progression will be a study priority.

 

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Related Service

miRNA/Small RNA Sequencing Service – miRNA sequencing is a new method and powerful tool to identify and quantitatively decode the entire population of microRNAs in your sample. LC Sciences now provides a comprehensive microRNA sequencing service. [Learn more…]

miRNA Microarray Service – LC Sciences provides a microRNA (miRNA) expression profiling service using microarrays based on our in-house developed µParaflo® technology platform. We have standard arrays for all mature miRNAs of all species available in the latest version of the miRBase database (Release 21, July 2014). Our service is comprehensive and includes sample labeling, array hybridization, image data processing and in-depth data analysis. Two-three weeks after receiving your total RNA samples, we’ll send you both the raw and fully analyzed data. [Learn more…]

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References

• M. Ciesla, K. Skrzypek, M. Kozakowska, A. Loboda, A. Jozkowicz, J. Dulak. (2011) MicroRNAs as biomarkers of disease onset. Anal Bioanal Chem 401,2051–2061. [abstract]
• K.C. Miranda, D.T. Bond, M. McKee, J. Skog, T.G. Păunescu, N. Da Silva, D. Brown, L.M. Russo. (2010) Nucleic acids within urinary exosomes/microvesicles are potential biomarkers for renal disease. Kidney Int 78, 191–199. [abstract]
• Gildea JJ, Carlson JM, Schoeffel CD, Carey RM, Felder RA. (2013) Urinary Exosome miRNome Analysis and its Applications to Salt Sensitivity of Blood Pressure. Clin Biochem 46(12):1131-4. [abstract]
• Haj-Ahmad TA, Abdalla MA, Haj-Ahmad Y. (2014) Potential Urinary miRNA Biomarker Candidates for the Accurate Detection of Prostate Cancer among Benign Prostatic Hyperplasia Patients. J Cancer 5(3), 182-191.[article]
• Liu Y, Silver C, Lee Y. (2015) Abstract 548: Exosome as biomarkers and diagnostics in bladder cancer. Cancer Research 75(15 Supplement), 548-548.[abstract]