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Autor(en) / Beteiligte

Titel

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

Ist Teil von

Ort / Verlag

England

Erscheinungsjahr

2015

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

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.

Sprache: Englisch
Identifikatoren: eISSN: 1476-4679
DOI: 10.1038/ncb3110
Titel-ID: cdi_pubmed_primary_25686251

Format: –
Schlagworte: Adenosine - metabolism, Adenosine Deaminase - genetics, Adenosine Deaminase - metabolism, Animals, Base Sequence, Cell Line, Tumor, Cyclic AMP Response Element-Binding Protein - genetics, Cyclic AMP Response Element-Binding Protein - metabolism, Disease Progression, Female, Gene Expression Regulation, Neoplastic, Genes, Reporter, Humans, Inosine - metabolism, Luciferases - genetics, Luciferases - metabolism, Melanoma - genetics, Melanoma - metabolism, Melanoma - pathology, Mice, Mice, Nude, MicroRNAs, Molecular Sequence Data, mRNA Cleavage and Polyadenylation Factors - genetics, mRNA Cleavage and Polyadenylation Factors - metabolism, Neoplasm Metastasis, Neoplasm Transplantation, RNA Editing, RNA-Binding Proteins - genetics, RNA-Binding Proteins - metabolism, Skin Neoplasms - genetics, Skin Neoplasms - metabolism, Skin Neoplasms - pathology, Transcription Factors - genetics, Transcription Factors - metabolism

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