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

Guermarie Velazquez-Torres, Einav Shoshan, Cristina Ivan, Li Huang, Enrique Fuentes-Mattei, Harrison Paret, Sun Jin Kim, Cristian Rodriguez-Aguayo, Victoria Xie, Denise Brooks, Steven J. M. Jones, A. Gordon Robertson, George Calin, Gabriel Lopez-Berenstein, Anil Sood and Menashe Bar-Eli ()
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Guermarie Velazquez-Torres: Unit 1906, The University of Texas MD Anderson Cancer Center
Einav Shoshan: Unit 1906, The University of Texas MD Anderson Cancer Center
Cristina Ivan: Unit 1362, The University of Texas MD Anderson Cancer Center
Li Huang: Unit 1906, The University of Texas MD Anderson Cancer Center
Enrique Fuentes-Mattei: Unit 1950, The University of Texas MD Anderson Cancer Center
Harrison Paret: Unit 1906, The University of Texas MD Anderson Cancer Center
Sun Jin Kim: Unit 1906, The University of Texas MD Anderson Cancer Center
Cristian Rodriguez-Aguayo: Unit 1950, The University of Texas MD Anderson Cancer Center
Victoria Xie: The University of Texas MD Anderson Cancer Center
Denise Brooks: Canada’s Michael Smith Cancer Agency
Steven J. M. Jones: Canada’s Michael Smith Cancer Agency
A. Gordon Robertson: Canada’s Michael Smith Cancer Agency
George Calin: Unit 1950, The University of Texas MD Anderson Cancer Center
Gabriel Lopez-Berenstein: Unit 1950, The University of Texas MD Anderson Cancer Center
Anil Sood: Unit 1362, The University of Texas MD Anderson Cancer Center
Menashe Bar-Eli: Unit 1906, The University of Texas MD Anderson Cancer Center

Nature Communications, 2018, vol. 9, issue 1, 1-7

Abstract: Abstract 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.

Date: 2018
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DOI: 10.1038/s41467-018-02851-7

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