miR-146a promotes the initiation and progression of melanoma by activating Notch signaling

Academic Article

Abstract

  • Oncogenic mutations in BRAF and NRAS occur in 70% of melanomas. In this study, we identify a microRNA, miR-146a, that is highly upregulated by oncogenic BRAF and NRAS. Expression of miR-146a increases the ability of human melanoma cells to proliferate in culture and form tumors in mice, whereas knockdown of miR-146a has the opposite effects. We show these oncogenic activities are due to miR-146a targeting the NUMB mRNA, a repressor of Notch signaling. Previous studies have shown that pre-miR-146a contains a single nucleotide polymorphism (C>G rs2910164). We find that the ability of pre-miR-146a/G to activate Notch signaling and promote oncogenesis is substantially higher than that of pre-miR-146a/C. Analysis of melanoma cell lines and matched patient samples indicates that during melanoma progression pre-miR-146a/G is enriched relative to pre-miR-146a/C, resulting from a C-to-G somatic mutation in pre-miR-146a/C. Collectively, our results reveal a central role for miR-146a in the initiation and progression of melanoma. © Forloni et al.
  • Published In

  • eLife  Journal
  • Digital Object Identifier (doi)

    Pubmed Id

  • 26537770
  • Author List

  • Forloni M; Dogra SK; Dong Y; Conte D; Ou J; Zhu LJ; Deng A; Mahalingam M; Green MR; Wajapeyee N
  • Volume

  • 2014
  • Issue

  • 3