Abstract PR05: Control of the melanoma metastatic phenotype by A-to-I microRNA editing

Abstract

Abstract Although recent studies have shown that adenosine-to-inosine (A-to-I) RNA editing occurs in microRNAs, its effects on tumor growth and metastasis are not well understood. We present evidence of CREB-mediated low expression of ADAR1 in metastatic melanoma cell lines and tumor specimens. Re-expression of ADAR1 resulted in the suppression of melanoma growth and metastasis in vivo. Consequently, we identified 3 miRs (miR-455-5P, mir-378-3P, miR-324-5P) undergoing A-to-I editing in the low-metastatic melanoma cell lines but not in highly metastatic. One of these miRs, miR-455-5P has two A-to-I RNA editing sites. The biological function of edited miR-455-5P is different from the unedited form. Indeed, w.t. miR-455 promotes melanoma metastasis via inhibition of the tumor suppressor gene CPEB1 . Moreover, w.t. miR-455 enhances melanoma growth and metastasis in vivo while the edited form inhibits these features mainly by affecting the tumor microenvironment. TCGA analysis confirmed accumulation of wild-type miR-455 in metastatic melanoma lesions. These results demonstrate a previously unrecognized role of RNA editing in melanoma progression. Citation Format: Einav Shoshan, Li Huang, Mayra E. Vasquez, Ho-Jeong Lee, Sun-Jin Kim, Cristina Ivan, George A. Calin, Anil K. Sood, Patrick Hwu, Jeffrey E. Gershenwald, Gal Markel, Isaiah J. Fidler, Menashe Bar-Eli. Control of the melanoma metastatic phenotype by A-to-I microRNA editing. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr PR05.