lncRNA NEAT1 facilitates melanoma cell proliferation, migration, and invasion via regulating miR-495-3p and E2F3

J Cell Physiol. 2019 Nov;234(11):19592-19601. doi: 10.1002/jcp.28559. Epub 2019 Jun 7.

Abstract

Melanoma contributes a lot to skin cancer-related deaths. lncRNAs are implicated in various diseases, including melanoma. lncRNA NEAT1 is frequently dysregulated and can play important roles in multiple cancers. Nevertheless, little has been studied about the function of NEAT1 in melanoma progression. In our present research, we displayed NEAT1 was overexpressed in melanoma cells. A series of functional assays showed that overexpression of NEAT1 promoted the proliferation, migration, and invasion of melanoma cells. By contrast, NEAT1 knockdown obviously restrained melanoma cell progression. Mechanistically, it was revealed that NEAT1 could directly bind with miR-495-3p, which led to a negative effect on miR-495-3p levels. In addition, miR-495-3p was significantly decreased in melanoma cells. Furthermore, E2F3 was postulated as the target of miR-495-3p and overexpression of this miR could suppress the levels of E2F3. Meanwhile, it was exhibited that melanoma cell proliferation, migration, and invasion induced by E2F3 silence was abrogated by miR-495-3p. Moreover, an in vivo xenograft nude mice model was established using A375 cells and it was indicated that NEAT1 promoted melanoma progression in vivo via regulating the miR-495-3p/E2F3 axis. In conclusion, we suggest that NEAT1 exerts an oncogenic effect on melanoma development via inhibition of miR-495-3p and induction of E2F3. NEAT1 might serve as a crucial prognostic biomarker of melanoma.

Keywords: E2F3; NEAT1; melanoma; miR-495-3p.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Biomarkers, Tumor / genetics
  • Carcinogenesis / genetics
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • E2F3 Transcription Factor / genetics*
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Knockdown Techniques
  • HCT116 Cells
  • Heterografts
  • Humans
  • Melanoma / genetics*
  • Melanoma / pathology
  • Mice
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • RNA, Long Noncoding / genetics*

Substances

  • Biomarkers, Tumor
  • E2F3 Transcription Factor
  • E2F3 protein, human
  • MIRN495 microRNA, human
  • MicroRNAs
  • NEAT1 long non-coding RNA, human
  • RNA, Long Noncoding