Abstract 3172: Role of miRNA-211in melanocytes and melanoma

Abstract

Abstract MicroRNAs (miRNAs) are small non-coding 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-211, which maps to the sixth intron of TRPM1 gene (a suppressor of melanoma metastasis), is highly expressed in primary 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. Inhibition of miRNA-211 expression by anti-miR211 inhibited intercellular Ca+2 update and the growth of rapidly growing melanocytes. Ectopic expression of miRNA-211in melanoma cells inhibit growth and reduced their migration. Regulation of miRNA-211 and its function in melanocytes and melanoma have not been well understood. We show that ectopic expression of p53 (a tumor suppressor) in melanocytes increase miRNA-211 expression and decrease TRPM1 expression. Inhibition of miRNA-211 did not change TPRM1 expression in melanocytes. Additionally, we show that 1.4 kb intron 6 genomic region of TRPM1 which contain miRNA-211 region is sufficient to activate miRNA-211 expression. And 1.4 kb of 6th intron luciferase reporter plasmid transfection followed by luciferase assay showed increase in promoter driven luciferase activity. These data suggests that the presence of putative promoter region of miRNA-211 in the sixth intron of TRPM1 gene. 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 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3172. doi:1538-7445.AM2012-3172