Abstract
Merkel cell carcinoma (MCC) is a rare and aggressive type of skin cancer associated with a poor prognosis. This carcinoma was named after its presumed cell of origin, the Merkel cell, which is a mechanoreceptor cell located in the basal epidermal layer of the skin. Merkel cell polyomavirus seems to be the major causal factor for MCC because approximately 80% of all MCCs are positive for viral DNAs. UV exposure is the predominant etiological factor for virus-negative MCCs. Intracellular microRNA analysis between virus-positive and virus-negative MCC cell lines and tumor samples have identified differentially expressed microRNAs. Comparative microRNA profiling has also been performed between MCCs and other non-MCC tumors, but not between normal Merkel cells and malignant Merkel cells. Finally, Merkel cell polyomavirus encodes one microRNA, but its expression in virus-positive MCCs is low, or non-detectable or absent, jeopardizing its biological relevance in tumorigenesis. Here, we review the results of microRNA studies in MCCs and discuss the potential application of microRNAs as biomarkers for the diagnosis, progression and prognosis, and treatment of MCC.
Highlights
Merkel cell carcinoma (MCC) is a rare and aggressive type of skin cancer associated with a poor prognosis
Whereas the virus is found in an episomal state in non-malignant cells, a characteristic for all virus-positive MCC tumors is that the viral genome is integrated into a clonal pattern, and that a non-sense mutation is present in the large T-antigen (LTAg)-encoding gene encoding a C-terminal truncated protein
This differential expression of these miRNAs was confirmed by quantitative reverse transcriptase PCR on a total RNA isolated from 20 MCC samples and from the Merkel cell polyomavirus (MCPyV)-positive MS-1 MCC cell line
Summary
MicroRNAs (miRNAs) are ~18–24 nucleotides long, non-coding RNA molecules encoded by the genomes of viruses, protists, plants and animals [1]. Extracellular miRNAs in complex with proteins have been described [12]. These circulating miRNAs can be taken up by recipient cells, and in this way, play a role in intercellular communication [13]. Plasma from healthy blood donors and media from cell cultures were shown to contain miRNAs associated with the protein argonaute 2 (Ago2), and Ago2-miRNA complexes were stable for at least two months at room temperature. In particular, interest in identifying circulating miRNAs as prognostic and diagnostic markers is growing. Both mature miRNA and isomiR profiles may be used as biomarkers [36]
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