Reduced adenosine-to-inosine miR-455-5p editing promotes melanoma growth and metastasis

Einav Shoshan, Aaron K. Mobley, Russell R. Braeuer, Takafumi Kamiya, Li Huang, Mayra E. Vasquez, Ahmad Salameh, Ho Jeong Lee, Sun Jin Kim, Cristina Ivan, Guermarie Velazquez-Torres, Ka Ming Nip, Kelsey Zhu, Denise Brooks, Steven J.M. Jones, Inanc Birol, Maribel Mosqueda, Yu Ye Wen, Agda Karina Eterovic, Anil K. SoodPatrick Hwu, Jeffrey E. Gershenwald, A. Gordon Robertson, George A. Calin, Gal Markel, Isaiah J. Fidler, Menashe Bar-Eli*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Although recent studies have shown that adenosine-to-inosine (A-to-I) RNA editing occurs in microRNAs (miRNAs), its effects on tumour growth and metastasis are not well understood. We present evidence of CREB-mediated low expression of ADAR1 in metastatic melanoma cell lines and tumour specimens. Re-expression of ADAR1 resulted in the suppression of melanoma growth and metastasis in vivo. Consequently, we identified three miRNAs undergoing A-to-I editing in the weakly metastatic melanoma but not in strongly metastatic cell lines. One of these miRNAs, miR-455-5p, has two A-to-I RNA-editing sites. The biological function of edited miR-455-5p is different from that of the unedited form, as it recognizes a different set of genes. Indeed, wild-type miR-455-5p promotes melanoma metastasis through inhibition of the tumour suppressor gene CPEB1. Moreover, wild-type miR-455 enhances melanoma growth and metastasis in vivo, whereas the edited form inhibits these features. These results demonstrate a previously unrecognized role for RNA editing in melanoma progression.

Original languageEnglish
Pages (from-to)311-321
Number of pages11
JournalNature Cell Biology
Volume17
Issue number3
DOIs
StatePublished - 2 Mar 2015

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