Epstein-Barr virus-encoded microRNA BART15-3p promotes cell apoptosis partially by targeting BRUCE

Hoyun Choi1, Hanna Lee, Sae Rom Kim

  • 1Research Institute of Immunobiology, Department of Medical Lifescience, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Journal of Virology
|May 17, 2013
PubMed

Insights

Epstein-Barr Virus microRNA miR-BART15-3p inhibits cell proliferation and promotes apoptosis by targeting the BRUCE protein. This viral microRNA is secreted in exosomes from infected cells.

Area of Science:

  • Virology
  • Molecular Biology
  • Cancer Research

Background:

  • Epstein-Barr Virus (EBV) encodes numerous microRNAs (miRNAs) from BART transcripts.
  • The functions of most BART miRNAs, including miR-BART15-3p, are largely uncharacterized.
  • EBV infection is associated with various cancers, including gastric carcinoma.

Purpose of the Study:

  • To investigate the function of BART-derived microRNA miR-BART15-3p.
  • To identify the molecular targets of miR-BART15-3p.
  • To explore the role of miR-BART15-3p in EBV-infected cells and its potential involvement in cancer.

Main Methods:

  • Cell proliferation assays and apoptosis assays (Annexin V, propidium iodide staining).
  • Bioinformatic analysis to predict miRNA targets.
  • Luciferase reporter assays and mutation studies to validate target interaction.
  • Western blotting to assess protein levels and qRT-PCR for mRNA levels.
  • Exosome isolation and characterization.

Main Results:

  • miR-BART15-3p significantly inhibited cell proliferation and induced apoptosis in EBV-infected cells.
  • Bioinformatic analysis predicted several anti-apoptotic targets; luciferase assays confirmed BRUCE as a direct target via its 3' UTR.
  • miR-BART15-3p downregulated BRUCE protein levels post-transcriptionally, without affecting mRNA levels.
  • miR-BART15-3p was secreted from gastric carcinoma cells, with higher concentrations found in exosomes.

Conclusions:

  • miR-BART15-3p induces apoptosis, at least partially, by inhibiting the translation of the apoptosis inhibitor BRUCE.
  • The findings reveal a novel mechanism by which EBV miRNAs can modulate host cell processes.
  • miR-BART15-3p's secretion and targeting of BRUCE suggest its potential role in EBV pathogenesis and cancer development.

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