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.
Highlights
We reported that metastatic melanoma cell lines and tumor specimens have reduced expression of ADAR1 and are deficient in their ability to perform miRNAs A-to-I editing
We found that the edited form preferentially targets the oncogene PARVA preventing the progression of melanoma towards the malignant phenotype
We have reported that ADAR1 expression is reduced in metastatic melanoma cell lines and in clinical metastatic melanoma specimens[9]
Summary
We have reported that metastatic melanoma cell lines and tumor specimens have reduced expression of ADAR1 and are impaired in their ability to perform A-to-I microRNA (miRNA) editing. The edited form of miR-378a-3p preferentially binds to the 3′-UTR of the PARVA oncogene and inhibits its expression, preventing the progression of melanoma towards the malignant phenotype. Edited miR-378a-3p but not its WT form inhibits melanoma metastasis in vivo. We reported that metastatic melanoma cell lines and tumor specimens have reduced expression of ADAR1 and are deficient in their ability to perform miRNAs A-to-I editing. We found that the edited form (expressed in non-metastatic cells) preferentially targets the oncogene PARVA preventing the progression of melanoma towards the malignant phenotype. We report on a novel epigenetic mechanism regulating the expression of PARVA, and affecting melanoma progression
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