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- Title
Reduced adenosine-to-inosine miR-455-5p editing promotes melanoma growth and metastasis.
- Authors
Shoshan, Einav; Mobley, Aaron K.; Braeuer, Russell R.; Kamiya, Takafumi; Huang, Li; Vasquez, Mayra E.; Salameh, Ahmad; Lee, Ho Jeong; Kim, Sun Jin; Ivan, Cristina; Velazquez-Torres, Guermarie; Nip, Ka Ming; Zhu, Kelsey; Brooks, Denise; Jones, Steven J. M.; Birol, Inanc; Mosqueda, Maribel; Wen, Yu-ye; Eterovic, Agda Karina; Sood, Anil K.
- 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.
- Subjects
ADENOSINES; MESSENGER RNA; TUMOR growth; METASTASIS; GENE expression
- Publication
Nature Cell Biology, 2015, Vol 17, Issue 3, p311
- ISSN
1465-7392
- Publication type
Article
- DOI
10.1038/ncb3110