The clinical relevance of circulating, exosomal miRNAs as biomarkers for cancer

Abstract

In cancer, deregulated expression levels of miRNAs are associated with tumorigenesis, tumor progression, metastasis and drug resistance. Apart from their release by apoptotic and necrotic cells, miRNAs can also be actively secreted into the blood circulation by exosomes. Exosomal miRNAs are thought to play an important role in cell-to-cell communication. Based on their biological functions and the possibility of quantifying miRNAs in patient blood in real time, these small non-coding RNA molecules may be a new promising class of potential non-invasive biomarkers. Screening of these liquid biopsies may provide information on target molecules of miRNAs and aberrant signaling pathways that can be blocked by a chosen targeted therapy. Consequently, therapy-associated modulations may facilitate treatment decisions. The present article discusses the potential clinical use of exosomal miRNAs as diagnostic and prognostic tumor markers. The emerging role of exosomes as a mediator of cell-to-cell signaling, to transfer miRNAs between cells, is also discussed.

Keywords:

• cell-to-cell communication
• diagnosis
• exosomes
• miRNAs
• prognosis
• signal pathways

Financial & competing interests disclosure

The author is supported by ERC (European Research Council) Advanced Investigator Grant (ERC-2010 AsG 20100317 DISSECT). The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Blood of cancer patients constitutes a pool of miRNAs that are either protein-bound or secreted in various extracellular vesicles, such as exosomes and apoptotic bodies, and derived from different sources, such as cancer and wild-type cells.

• MiRNAs, a family of small non-coding RNAs, repress translation of hundreds of mRNAs and, thus, are involved in multiple signal pathways.

• Exosomes mediate cell-to-cell communication by transferring proteins, nucleic acids and lipids between cells.

• Profiling of exosomal miRNAs, that can be performed in diverse body fluids in real-time and in the absence of tumor tissue, may reflect the pathology and dynamics of diseases.

• Exosomes can also be used as targeted drug delivery vehicles and entered clinical trials for different diseases.

Notes