MicroRNA let-7b targets important cell cycle molecules in malignant melanoma cells and interferes with anchorage-independent growth

• Published in: Cell research Vol. 18; no. 5; pp. 549 - 557
• Main Authors: Schultz, Julia, Lorenz, Peter, Gross, Gerd, Ibrahim, Saleh, Kunz, Manfred
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2008; Nature Publishing Group
• Subjects: Biomedical and Life Sciences; Cell Biology; Cell Cycle - genetics; Cyclin A - genetics; Cyclin A - metabolism; Cyclin D1 - genetics; Cyclin D1 - metabolism; Cyclins - genetics; Cyclins - metabolism; Fluorescent Antibody Technique; Humans; Immunoblotting; Life Sciences; Melanoma; Melanoma - genetics; Melanoma - metabolism; Melanoma - pathology; MicroRNAs - genetics; original-article; Polymerase Chain Reaction; Tumors; 基因表达; 恶性皮肤瘤; 皮肤癌; 细胞周期; reactivation of gene expression; melanoma/skin cancer; cell cyle; cyclins; silencing
• ISSN: 1001-0602; 1748-7838
• DOI: 10.1038/cr.2008.45

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 oflet-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.