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

• 来源期刊: 细胞研究（英文版）
• 年，卷（期）: 2008,（5）
• 页码范围: 549-557
• 页数: 9页
• 语种: 英文

摘要

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 DI.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.