EBV miR-BART10-3p Promotes Cell Proliferation and Migration by Targeting DKK1

Int J Biol Sci. 2019 Jan 24;15(3):657-667. doi: 10.7150/ijbs.30099. eCollection 2019.

Abstract

In Epstein-Barr virus (EBV)-infected epithelial cancers, BamHI A rightward transcript (BART) miRNAs are highly expressed. However, only a few target genes of BART miRNAs have been investigated. Our mRNA microarray data showed that DKK1 was markedly down-regulated in EBV-associated gastric carcinoma (EBVaGC) cells. Using luciferase reporter assay we tested whether miR-BART10-3p regulates DKK1 by directly targeting the 3'-UTR of DKK1 mRNA. We observed that miR-BART10-3p transfection decreased DKK1 expression, while an LNA inhibitor of miR-BART10-3p (LNA-miR-BART10-3p(i)) increased DKK1 expression. Furthermore, miR-BART10-3p and siDKK1 promoted cell proliferation and migration. In contrast, transfecting GC cells with LNA-miR-BART10-3p(i) or DKK1 over expression vector suppressed cell proliferation and migration. Our results suggest that miR-BART10-3p may be involved in the tumor progression of EBVaGC by targeting DKK1.

Keywords: BART miRNA; DKK1; Epstein-Barr virus; cell migration; cell proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Movement / physiology*
  • Cell Proliferation / genetics
  • Cell Proliferation / physiology*
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Expression Regulation, Neoplastic / physiology
  • Herpesvirus 4, Human / genetics*
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Wound Healing / genetics
  • Wound Healing / physiology

Substances

  • DKK1 protein, human
  • Intercellular Signaling Peptides and Proteins
  • MicroRNAs