¹Institute of Pathology, University of Regensburg, Franz-Josef-Strauss-Allee 11, Regensburg, Germany

Correspondence: Professor Dr A-K Bosserhoff, Institute of Pathology, University of Regensburg, Franz-Josef-Strauss-Allee 11, Regensburg, Bavaria D-93053, Germany. E-mail: anja.bosserhoff@klinik.uni-regensburg.de

Received 18 February 2008; Revised 10 July 2008; Accepted 14 July 2008; Published online 4 August 2008.

Abstract

Although integrin ₃ is known to play an important role in melanoma progression and invasion, regulation of integrin ₃ expression in melanoma has not been analysed in detail until today. As transcriptional regulation of integrin ₃ 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 ₃ mRNA. Transfection of melanoma cells with let-7a pre-miR^TM molecules resulted in the downregulation of integrin ₃ mRNA and protein expression. In addition, we cloned the 3'-UTR of the integrin ₃ 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 ₃ 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 ₃ 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 ₃ expression and showed that the loss of let-7a expression is involved in development and progression of malignant melanoma.