Integrin β3 expression is regulated by let-7a miRNA in malignant melanoma

Abstract

Although integrin β3 is known to play an important role in melanoma progression and invasion, regulation of integrin β3 expression in melanoma has not been analysed in detail until today. As transcriptional regulation of integrin β3 was ruled out by our analysis, we concentrated on the regulation by microRNAs (miRNAs). Comparing primary melanocytes and malignant melanoma cell lines, we found that one candidate miRNA, miR-let-7a, was lost in melanoma and sequence analysis suggested an interaction with the 3′-untranslated region (3′-UTR) of integrin β3 mRNA. Transfection of melanoma cells with let-7a pre-miRTM molecules resulted in the downregulation of integrin β3 mRNA and protein expression. In addition, we cloned the 3′-UTR of the integrin β3 mRNA containing the let-7a target sequence into a reporter plasmid and revealed that let-7a negatively regulates reporter gene expression. The repressed expression of integrin β3 accompanies with reduced invasive potential of melanoma cells transfected with synthetic let-7a molecules observed in Boyden chamber assays. On the other hand, the induction of integrin β3 expression was achieved in melanocytes by transfection with let-7a anti-miRs, resulting in invasive behavior of transfected melanocytes. In summary, we determined miRNA let-7a to be an important regulator of integrin β3 expression and showed that the loss of let-7a expression is involved in development and progression of malignant melanoma. © 2008 Macmillan Publishers Limited All rights reserved.