Abstract

Abstract MicroRNAs (miRNAs) are regulatory RNAs that regulate gene expression. Evidence is accumulating that miRNAs are involved in almost all aspects of tumor biology including tumor cell survival, proliferation and migration. Here, we report that miRNA-221, which maps to the sixth intron of TRPM1 gene (a suppressor of melanoma metastasis), is highly expressed in melanocytes and its expression is reduced in primary and metastatic melanoma cell lines. Expression of miRNA-211 correlates with expression of TRPM1, a transient receptor potential family member calcium channel protein that we showed to be involved in regulation of melanocyte calcium homeostasis and melanin pigmentation. TRPM1and miRNA-211 expression are significantly lower in rapidly proliferative melanocytes compared to the slow growing, differentiated melanocytes. Expression of RAB22A (member of the RAS family of small GTPases), a predicted RNA target of miRNA-211is inversely correlated with the expression of miRNA-211and TRPM1 in melanocytes. Inhibition of miRNA-211 expression by anti-miR211 inhibited the growth of rapidly growing melanocytes. Ectopic expression of miRNA-211in melanoma cells inhibit growth and reduced their migration. We propose that activation of endogenous miRNA-211 expression or targeted delivery of miR-211 in melanoma is a potential therapeutic option for treatment of cutaneous melanoma. 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 3957. doi:10.1158/1538-7445.AM2011-3957

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