title: TAX1BP1 downregulation by EBV-miR-BART15-3p enhances chemosensitivity of gastric cancer cells to 5-FU.
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.
authors.affiliation: Department of Medical Lifescience, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.
authors.forename: Hoyun
authors.initials: H
authors.lastname: Choi
authors.affiliation: Department of Medical Lifescience, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea. sukklee@catholic.ac.kr.
authors.forename: Suk Kyeong
authors.identifier: http://orcid.org/0000-0002-3751-7682
authors.initials: SK
authors.lastname: Lee
mesh_terms: D020413:3' Untranslated Regions; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D001483:Base Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D005472:Fluorouracil / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology / Q000821:virology; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D020413:3' Untranslated Regions; D000964:Antimetabolites, Antineoplastic; C401541:BIRC6 protein, human; D051034:Inhibitor of Apoptosis Proteins; D047908:Intracellular Signaling Peptides and Proteins; D035683:MicroRNAs; D016328:NF-kappa B; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D012367:RNA, Viral; C120635:TAX1BP1 protein, human; D008156:Luciferases; D005472:Fluorouracil