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A-to-I miR-378a-3p editing can prevent melanoma progression via regulation of PARVA expression

2018; Nature Portfolio; Volume: 9; Issue: 1 Linguagem: Inglês

10.1038/s41467-018-02851-7

2041-1723

Guermarie Velázquez-Torres, Einav Shoshan, Cristina Ivan, Li Huang, Enrique Fuentes‐Mattei, Harrison Paret, Sun Jin Kim, Cristian Rodriguez‐Aguayo, Victoria K. Xie, Denise Brooks, Steven J.M. Jones, A. Gordon Robertson, George A. Călin, Gabriel López-Berenstein, Anil K. Sood, Menashe Bar‐Eli,

CRISPR and Genetic Engineering

Previously we have reported that metastatic melanoma cell lines and tumor specimens have reduced expression of ADAR1 and consequently are impaired in their ability to perform A-to-I microRNA (miRNA) editing. The effects of A-to-I miRNAs editing on melanoma growth and metastasis are yet to be determined. Here we report that miR-378a-3p is undergoing A-to-I editing only in the non-metastatic but not in metastatic melanoma cells. The function of the edited form is different from its wild-type counterpart. The edited form of miR-378a-3p preferentially binds to the 3'-UTR of the PARVA oncogene and inhibits its expression, thus preventing the progression of melanoma towards the malignant phenotype. Indeed, edited miR-378a-3p but not its WT form inhibits melanoma metastasis in vivo. These results further emphasize the role of RNA editing in melanoma progression.