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

Nat Commun. 2018 Jan 31;9(1):461. doi: 10.1038/s41467-018-02851-7.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Adenosine / genetics*
  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Disease Progression
  • Epigenesis, Genetic
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Inosine / genetics*
  • Melanoma / genetics
  • Melanoma / pathology*
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • Microfilament Proteins / genetics*
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Oncogenes
  • RNA Editing*
  • Skin Neoplasms / genetics
  • Skin Neoplasms / pathology*

Substances

  • 3' Untranslated Regions
  • MIRN378 microRNA, human
  • MicroRNAs
  • Microfilament Proteins
  • PARVA protein, human
  • Inosine
  • Adenosine