Cancer Letters

Cancer Letters

Volume 347, Issue 1, 28 May 2014, Pages 29-37
Cancer Letters

Mini-review
MiRNA in melanoma-derived exosomes

https://doi.org/10.1016/j.canlet.2014.02.004Get rights and content

Abstract

Proteins, RNAs and viruses can be spread through exosomes, therefore transport utilizing these nanovesicles is of the great interest. MiRNAs are common exosomal constituents capable of influencing expression of a variety of target genes. MiRNA signatures of exosomes are unique in cancer patients and differ from those in normal controls. The knowledge about miRNA profiles of tumor-derived exosomes may contribute to better diagnosis, determination of tumor progression and response to treatment, as well as to the development of targeted therapies. We summarize the current knowledge with regard to miRNAs that are found in exosomes derived from tumors, particularly from melanoma.

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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