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Abstract
Sir,
We would like to congratulate Völler et al (2013) on their recent study showing an
unchanged mRNA AGO2 expression in melanoma and a strong reduction of AGO2 expression
on protein level. This goes along with the findings in our study on the miRNA processing
machinery performed in melanoma, which likewise has previously shown an unchanged
mRNA AGO2 expression level in melanoma (Sand et al, 2012c). Interestingly, in contrast
to melanoma skin cancer, mRNA AGO2 expression levels in epithelial skin cancer (both
cutaneous squamous cell and basal cell carcinoma) were significantly higher (P<0.05)
compared with healthy controls (Sand et al, 2010, 2012a, 2012b). Although we do agree
with the authors that a deregulation of microRNA (miRNA) was observed in several types
of cancer and particularly in skin cancer, with reference to our previous studies
we do not agree that changes in the miRNA processing enzymes have not been analysed
until today as stated in their abstract (Sand et al, 2009, 2011, 2012d, 2012e, 2013;
2014; Sand and Skrygan, 2014).
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.
MicroRNAs (miRNAs) are very small endogenous RNA molecules about 22-25 nucleotides in length, capable of post-transcriptional gene regulation. miRNAs bind to their target messenger RNAs (mRNAs), leading to cleavage or suppression of target mRNA translation based on the degree of complementarity. miRNAs have recently been shown to play pivotal roles in diverse developmental and cellular processes and linked to a variety of skin diseases and cancers. Disruption of miRNA metabolism is also involved in wound healing and inflammatory skin conditions. Here, we review the role of miRNAs in cutaneous biology.
[1
]Dermatologic Surgery Unit, Department of Dermatology, Venereology and Allergology,
Ruhr-University Bochum , Gudrunstrasse 56, 44791 Bochum, Germany
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