Abstract 1442: Expression of miRNA processing factor Dicer in cutaneous melanoma and its role in cell invasion

Abstract

Abstract Deregulated expression of miRNAs is a hallmark of various human cancers. One potential mechanism for the aberrant expression of miRNAs in cancers is their abnormal processing due to altered expression or function of their processing factors such as Dicer and Drosha. Although altered expression of several miRNAs have been reported in melanoma, the expression profile of miRNA processing factors in this cancer is unknown. In this study we examined the expression of Dicer protein in different stages of melanocytic lesions. Using tissue microarray and immunohistochemistry, we evaluated cytoplasmic Dicer expression in 32 dysplastic nevi, 77 primary melanomas, and 48 metastatic melanomas. Our data revealed that expression of Dicer has a significant but inverse correlation with progression of melanoma (P < 0.001). Accordingly, the number of samples with moderate-strong staining for Dicer was reduced from 81.2% in dysplastic nevi to 67.5% in primary melanoma and 40.8% in metastatic melanoma. The expression of Dicer was also negatively correlated with the American Joint Committee on Cancer (AJCC) staging of the melanoma samples (p=0.019). Moreover, the reduced Dicer expression was correlated with a poorer disease-specific 5-year survival of melanoma patients (P = 0.026). Multivariate Cox regression analysis revealed that reduced nuclear Dicer expression is an independent prognostic factor to predict patient outcome (P = 0.030). We also knocked down Dicer expression and used Boyden chamber migration assay to study its role in the invasion ability of MMRU human melanoma cells. Interestingly, knockdown of Dicer enhanced the invasion ability of MMRU cells by 2-fold. Our results demonstrate the critical role of miRNA machinery in the progression of melanoma, suggesting that Dicer may be a suitable prognostic marker for human melanoma patients as well as a potential therapeutic target. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1442. doi:10.1158/1538-7445.AM2011-1442