Mini-reviewMiRNA in melanoma-derived exosomes
Section snippets
Short characterization of biogenesis, structure and composition of exosomes
Exosomes are small, intraluminal vesicles (30–150 nm in diameter), that were first described by Trams and coworkers [1]. Many cell types release exosomes, including reticulocytes, B and T cells, dendritic cells, mast cells and epithelial cells, as well as tumor cells [2], [3], [4] Exosomes have been detected in most body fluids [5], [6]. They are composed of a lipid bilayer membrane containing ceramides, cholesterol, sphingolipids and phosphoglycerides [7], [8], [9]. Exosomes are enriched with a
Exosomes as miRNA carrying vesicles
Exosomal transfer of mRNAs and miRNAs has been recognized as an important cellular communication system for the exchange of genetic and epigenetic information between cells [5], [40], [42]. MiRNAs (microRNAs) are small (19–25 nt), non-coding regulatory RNAs. The miRBase database which contains information for miRNAs (release 20, http://www.mirbase.org) lists 24521 entries representing hairpin precursor miRNAs, and 30424 mature miRNA products from 206 species. Among them are 1872 miRNAs from
MiRNAs and exosomes in tumor development
Aberrant miRNA expression is observed in many cancers when compared to their normal tissue counterparts [47], [65]. A possible role of miRNAs in cancer development was postulated when the influence of miRNAs on proliferation and apoptosis was observed in Caenorhabditis elegans and Drosophila [66], [67]. The expression of miRNAs in tumors is frequently dysregulated and miRNAs can function as oncogenes or tumor-suppressor genes [68]. Among the mechanisms leading to aberrant miRNA expression,
Exosomal miRNA in melanoma
Melanoma develops by the malignant transformation of melanocytes and is considered as the most aggressive form of skin cancer characterized by a high mortality rate. For the improvement of therapies it is necessary to determine the complex molecular mechanisms leading to melanoma. There is no doubt that miRNAs, as crucial post-transcriptional regulators of gene expression, are important components in melanoma biology [87], [88]. MiRNAs deregulate relevant transcription factors to control the
Exosomes as delivery system
There is great interest in exosome mediated transport, focusing on their role in delivery of their content across biological membranes [119], [120], [121], [122], [123], [124]. As exosomes are autologously generated within the host, they can become the non-immunogenic carriers of drugs, RNA or target proteins. Therefore, exosome-based therapies may become an attractive strategy against cancers and other diseases [10]. A study by Alvarez-Erviti et al. showed that systemically applied exosomes
Future directions
MiRNAs found in exosomes are characteristic for the cell from which these nanovesicles are released [5]. MiRNA signatures of circulating exosomes in cancer patients differ from those in normal controls [134]. Therefore, exosomal miRNAs might serve as diagnostic markers of cancer [5], [46], [63], [135], including melanoma [82]. Furthermore, due to the simplicity of isolation techniques of circulating exosomes, exosomal miRNA profile analysis might become a non-invasive tool for the detection of
Conflict of Interest
None declared.
Acknowledgements
The authors wish to thank Prof. S. Louise Cosby from Queen’s University Belfast for reviewing the manuscript and Ewa Wlazlowicz for her technical help. Research in the authors’ laboratories is supported by Grant 2012/05/B/NZ2/00574 from the National Science Centre. The content is solely the responsibility of the authors.
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