RNA Editing and Melanoma Metastasis

Einav Shoshan¹, Aaron K. Mobley¹ , Russell R. Braeuer¹,Takafumi Kamiya¹, Li Huang¹, Mayra Vasquez¹ , Ahmad Salameh², Ho Jeong Lee¹, Sun Jin Kim¹, Cristina Ivan³ , George A. Calin⁴, Anil K. Sood^1,3, Patrick Hwu⁵, Jeffrey E Gershenwald⁶, Gal Markel^7,8_, Isaiah J. Fidler¹, and Menashe Bar-Eli¹

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 undergoing A-to-I editing in the low-metastatic melanoma cell lines but not in highly metastatic. One of these miRs, miR-455 has two A-to-I RNA editing sites. The biological function of edited miR-455 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. 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.

Shoshan et al…Menashe Bar-Eli, Nat Cell Biol. 2015 Mar;17(3):311-21. doi: 10.1038/ncb3110. Epub 2015 Feb 16. PMID:25686251