Differential Expression Profiling of MicroRNAs in Human Cutaneous and Uveal Melanoma

Background: Over the past decade, microRNA (miRNA)-mediated epigenetic regulation of tumour suppressor genes and oncogenes has been shown to play a central role in melanomagenesis. Here, we examined the miRNA signature discriminating cutaneous and uveal melanoma. Methods: Genome-wide profiling of miRNAs was performed in cutaneous and uveal melanoma cell lines by human miRNA microarray platform (Agilent Sanger miRBase-release 10.1) with 723 human and 76 human viral miRNAs represented. Agilent Feature Extraction Software was used for background subtraction. LOWESS and Quantile normalizations were performed. miRNA microarray expression data were validated by RT-PCR. Results: Relative to normal melanocytes, in uveal melanoma cells, miR-130b, miR-193b, miR-320a, and miR-9* significantly decreased, and miR-654-3p markedly increased; in cutaneous melanoma cells, miR-199a-3p and miR-22 were down-regulated, whereas let-7g was up-regulated. Two of these miRNAs, mir-193b and let-7g, were previously shown as potential regulators in melanoma, whereas the other ones have not been related to melanoma yet. Conclusions: Our analysis enables us to identify miRNAs that have not previously been associated with melanoma. In addition, the comprehensive survey of differentially expressed miRNAs shows remarkable differences between cutaneous and uveal melanoma. Although the study is preliminary, we believe the results add to the present knowledge on miRNA dysregulation in melanoma carcinogenesis. As such the results would serve as a starting point for identifying the direct targets of key miRNAs and elucidating their mechanisms of regulation. Understanding the functional roles of miRNAs in melanoma will contribute to the development of targeted therapy.