Epstein-Barr virus miR-BART20-5p regulates cell proliferation and apoptosis by targeting BAD

Hyoji Kim1, Hoyun Choi1, Suk Kyeong Lee1

  • 1Department of Medical Lifescience, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 137-701, South Korea.

Cancer Letters
|December 3, 2014
PubMed

Insights

Epstein-Barr virus BART miRNAs are common in tumors. This study identifies miR-BART20-5p as a key player, showing it targets BAD to promote cancer growth and chemoresistance in EBV-associated gastric carcinoma.

Area of Science:

  • Molecular Biology
  • Virology
  • Oncology

Background:

  • Epstein-Barr virus (EBV) BamHI A rightward transcript (BART) microRNAs (miRNAs) are frequently detected in EBV-associated malignancies.
  • The specific functions of most BART miRNAs remain largely uncharacterized.

Purpose of the Study:

  • To investigate the role of BART miRNAs in EBV-associated gastric carcinoma.
  • To determine if BART miRNAs regulate the expression of Bcl-2-associated death promoter (BAD).

Main Methods:

  • Bioinformatic analysis to identify potential BART miRNA targets of BAD.
  • Luciferase reporter assays to confirm direct targeting of BAD by miR-BART20-5p.
  • Transfection experiments with miR-BART20-5p and its inhibitor to assess effects on BAD expression, apoptosis, cell proliferation, and chemoresistance.

Main Results:

  • Bioinformatics predicted five BART miRNAs could target BAD; miR-BART20-5p was the only one to reduce BAD expression upon transfection.
  • Luciferase assays confirmed direct interaction between miR-BART20-5p and the 3'-UTR of BAD.
  • miR-BART20-5p significantly decreased BAD mRNA and protein levels, reduced apoptosis, enhanced cell proliferation, and increased resistance to 5-fluorouracil and docetaxel.

Conclusions:

  • miR-BART20-5p directly targets BAD in EBV-infected cells.
  • This interaction contributes to the tumorigenesis of EBV-associated gastric carcinoma by promoting cell survival and chemoresistance.

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