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TAX1BP1 downregulation by EBV-miR-BART15-3p enhances chemosensitivity of gastric cancer cells to 5-FU

Authors
  • Choi, Hoyun1
  • Lee, Suk Kyeong1
  • 1 The Catholic University of Korea, Department of Medical Lifescience, College of Medicine, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea , Seoul (South Korea)
Type
Published Article
Journal
Archives of Virology
Publisher
Springer-Verlag
Publication Date
Oct 18, 2016
Volume
162
Issue
2
Pages
369–377
Identifiers
DOI: 10.1007/s00705-016-3109-z
Source
Springer Nature
Keywords
License
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Abstract

MicroRNAs (miRNAs) are a class of noncoding RNA molecules approximately 19 to 25 nucleotides in length that downregulate the expression of target genes at the post-transcriptional level by binding to the 3′-untranslated region (3’-UTR). Epstein-Barr virus (EBV) generates at least 44 miRNAs, but the functions of most of these miRNAs have not yet been identified. Previously, we reported BRUCE as a target of miR-BART15-3p, a miRNA produced by EBV, but our data suggested that there might be other apoptosis-associated target genes of miR-BART15-3p. Thus, in this study, we searched for new target genes of miR-BART15-3p using in silico analyses. We found a possible seed match site in the 3′-UTR of Tax1-binding protein 1 (TAX1BP1). The luciferase activity of a reporter vector including the 3′-UTR of TAX1BP1 was decreased by miR-BART15-3p. MiR-BART15-3p downregulated the expression of TAX1BP1 mRNA and protein in AGS cells, while an inhibitor against miR-BART15-3p upregulated the expression of TAX1BP1 mRNA and protein in AGS-EBV cells. Mir-BART15-3p modulated NF-κB activity in gastric cancer cell lines. Moreover, miR-BART15-3p strongly promoted chemosensitivity to 5-fluorouracil (5-FU). Our results suggest that miR-BART15-3p targets the anti-apoptotic TAX1BP1 gene in cancer cells, causing increased apoptosis and chemosensitivity to 5-FU.

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