Volume 18, No 5, May 2008
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 18 Issue 5, May 2008: 549-557
ORIGINAL ARTICLES
MicroRNA let-7b targets important cell cycle molecules in malignant melanoma cells and interferes with anchorage-independent growth
Julia Schultz1, Peter Lorenz2, Gerd Gross1, Saleh Ibrahim3 and Manfred Kunz1
1Department of Dermatology and Venereology, University of Rostock, 18055 Rostock, Germany
2Institute of Immunology and Proteome Center, University of Rostock, 18055 Rostock, Germany
3Department of Immunogenetics, University of Rostock, 18055 Rostock, Germany
Correspondence: Manfred Kunz(manfred.kunz@med.uni-rostock.de )
A microRNA expression screen was performed analyzing 157 different microRNAs in laser-microdissected tissues from benign melanocytic nevi (n = 10) and primary malignant melanomas (n = 10), using quantitative real-time PCR. Differential expression was found for 72 microRNAs. Members of the let-7 family of microRNAs were significantly downregulated in primary melanomas as compared with benign nevi, suggestive for a possible role of these molecules as tumor suppressors in malignant melanoma. Interestingly, similar findings had been described for lung and colon cancer. Overexpression of let-7b in melanoma cells in vitro downregulated the expression of cyclins D1, D3, and A, and cyclin-dependent kinase (Cdk) 4, all of which had been described to play a role in melanoma development. The effect of let-7b on protein expression was due to targeting of 3'-untranslated regions (3'UTRs) of individual mRNAs, as exemplified by reporter gene analyses for cyclin D1. In line with its downmodulating effects on cell cycle regulators, let-7b inhibited cell cycle progression and anchorage-independent growth of melanoma cells. Taken together, these findings not only point to new regulatory mechanisms of early melanoma development, but also may open avenues for future targeted therapies of this tumor.
Cell Research (2008) 18:549-557. doi: 10.1038/cr.2008.45; published online 1 April 2008
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