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Open AccessArticle

Ion Channel Expression in Human Melanoma Samples: In Silico Identification and Experimental Validation of Molecular Targets

1
Istituto Dermopatico dell’Immacolata (IDI-IRCCS), 00167 Rome, Italy
2
Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Unit of Histology and Medical Embryology, Sapienza University of Rome, 00161 Rome, Italy
3
Medical Oncology, Sapienza, University of Rome, 00161 Rome, Italy
4
Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità (ISS), 00161 Rome, Italy
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(4), 446; https://doi.org/10.3390/cancers11040446
Received: 5 March 2019 / Revised: 20 March 2019 / Accepted: 23 March 2019 / Published: 29 March 2019
(This article belongs to the Special Issue Ion Channels in Cancer)
Expression of 328 ion channel genes was investigated, by in silico analysis, in 170 human melanoma samples and controls. Ninety-one members of this gene-family (i.e., about 28%) show a significant (p < 0.05) differential expression in melanoma- vs. nevi-biopsies, taken from the GEO database. ROC (receiver operating characteristic) analysis selected 20 genes as potential markers showing the highest discrimination ability of melanoma vs. nevi (AUC > 0.90 and p < 0.0001). These 20 genes underwent a first in silico-validation round in an independent patients-dataset from GEO. A second-in silico-validation step was then carried out on a third human dataset in Oncomine. Finally, five genes were validated, showing extremely high sensitivity and specificity in melanoma detection (>90% in most cases). Such five genes (namely, SCNN1A, GJB3, KCNK7, GJB1, KCNN2) are novel potential melanoma markers or molecular targets, never previously related to melanoma. The “druggable genome” analysis was then carried out. Miconazole, an antifungal drug commonly used in clinics, is known to target KCNN2, the best candidate among the five identified genes. Miconazole was then tested in vitro in proliferation assays; it dose-dependently inhibited proliferation up to 90% and potently induced cell-death in A-375 and SKMEL-28 melanoma cells, while it showed no effect in control cells. Moreover, specific silencing of KCNN2 ion channel was achieved by siRNA transfection; under such condition miconazole strongly increases its anti-proliferative effect. In conclusion, the present study identified five ion channels that can potentially serve as sensitive and specific markers in human melanoma specimens and demonstrates that the antifungal drug miconazole, known to target one of the five identified ion channels, exerts strong and specific anti-melanoma effects in vitro. View Full-Text
Keywords: KCNN2; ion channels; melanoma; miconazole KCNN2; ion channels; melanoma; miconazole
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MDPI and ACS Style

D’Arcangelo, D.; Scatozza, F.; Giampietri, C.; Marchetti, P.; Facchiano, F.; Facchiano, A. Ion Channel Expression in Human Melanoma Samples: In Silico Identification and Experimental Validation of Molecular Targets. Cancers 2019, 11, 446. https://doi.org/10.3390/cancers11040446

AMA Style

D’Arcangelo D, Scatozza F, Giampietri C, Marchetti P, Facchiano F, Facchiano A. Ion Channel Expression in Human Melanoma Samples: In Silico Identification and Experimental Validation of Molecular Targets. Cancers. 2019; 11(4):446. https://doi.org/10.3390/cancers11040446

Chicago/Turabian Style

D’Arcangelo, Daniela; Scatozza, Francesca; Giampietri, Claudia; Marchetti, Paolo; Facchiano, Francesco; Facchiano, Antonio. 2019. "Ion Channel Expression in Human Melanoma Samples: In Silico Identification and Experimental Validation of Molecular Targets" Cancers 11, no. 4: 446. https://doi.org/10.3390/cancers11040446

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