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Comparative microarray analysis of microRNA expression profiles in primary cutaneous malignant melanoma, cutaneous malignant melanoma metastases, and benign melanocytic nevi
Authors:Michael Sand  Marina Skrygan  Daniel Sand  Dimitrios Georgas  Thilo Gambichler  Stephan A Hahn  Peter Altmeyer  Falk G Bechara
Institution:1. Department of Dermatology, Venereology and Allergology, Ruhr University Bochum, 44791, Bochum, Germany
4. Dermatologic Surgery Unit, Department of Dermatology, Venereology and Allergology, St. Josef Hospital, Ruhr University Bochum, Gudrunstrasse 56, 44791, Bochum, Germany
2. Department of Medicine, Olive View UCLA Medical Center, University of California, Los Angeles (UCLA), Los Angeles, CA 91342, USA
3. Department of Internal Medicine, Knappschaftskrankenhaus University of Bochum, Zentrum für Klinische Forschung, Labor für Molekulare Gastroenterologische Onkologie, 44780, Bochum, Germany
Abstract:Perturbations in microRNA (miRNA) expression profiles have been reported for cutaneous malignant melanoma (CMM) predominantly when examined in cell lines. Despite the rapidly growing number of newly discovered human miRNA sequences, the availability of up-to-date miRNA expression profiles for clinical samples of primary cutaneous malignant melanoma (PCMM), cutaneous malignant melanoma metastases (CMMM), and benign melanocytic nevi (BMN) is limited. Specimens excised from the center of tumors (lesional) from patients with PCMM (n=9), CMMM (n=4), or BMN (n=8) were obtained during surgery. An exploratory microarray analysis was performed by miRNA expression profiling based on Agilent platform screening for 1205 human miRNAs. The results from the microarray analysis were validated by TaqMan quantitative real-time polymerase chain reaction. In addition to several miRNAs previously known to be associated with CMM, 19 unidentified miRNA candidates were found to be dysregulated in CMM patient samples. Among the 19 novel miRNA candidates, the genes hsa-miR-22, hsa-miR-130b, hsa-miR-146b-5p, hsa-miR-223, hsa-miR-301a, hsa-miR-484, hsa-miR-663, hsa-miR-720, hsa-miR-1260, hsa-miR-1274a, hsa-miR-1274b, hsa-miR-3663-3p, hsa-miR-4281, and hsa-miR-4286 were upregulated, and the genes hsa-miR-24-1*, hsa-miR-26a, hsa-miR-4291, hsa-miR-4317, and hsa-miR-4324 were downregulated. The results of this study partially confirm previous CMM miRNA profiling studies identifying miRNAs that are dysregulated in CMM. However, we report several novel miRNA candidates in CMM tumors; these miRNA sequences require further validation and functional analysis to evaluate whether they play a role in the pathogenesis of CMM.
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