title: Epstein-Barr virus miR-BART20-5p regulates cell proliferation and apoptosis by targeting BAD.
abstract: Although Epstein-Barr virus (EBV) BamHI A rightward transcript (BART) microRNAs (miRNAs) are ubiquitously expressed in EBV-associated tumors, the role of most BART miRNAs is unclear. In this study, we showed that Bcl-2-associated death promoter (BAD) expression was significantly lower in EBV-infected AGS-EBV cells than in EBV-negative AGS cells and investigated whether BART miRNAs target BAD. Using bioinformatics analysis, five BART miRNAs showing seed match with the 3' untranslated region (3'-UTR) of BAD were selected. Of these, only miR-BART20-5p reduced BAD expression when individually transfected into AGS cells. A luciferase assay revealed that miR-BART20-5p directly targets BAD. The expression of BAD mRNA and protein was decreased by miR-BART20-5p and increased by an inhibitor of miR-BART20-5p. PE-Annexin V staining and cell proliferation assays showed that miR-BART20-5p reduced apoptosis and enhanced cell growth. Furthermore, miR-BART20-5p increased chemoresistance to 5-fluorouracil and docetaxel. Our data suggest that miR-BART20-5p contributes to tumorigenesis of EBV-associated gastric carcinoma by directly targeting the 3'-UTR of BAD.
authors.affiliation: Department of Medical Lifescience, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 137-701, South Korea.
authors.forename: Hyoji
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Medical Lifescience, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 137-701, South 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 137-701, South Korea. Electronic address: sukklee@catholic.ac.kr.
authors.forename: Suk Kyeong
authors.initials: SK
authors.lastname: Lee
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005472:Fluorouracil / Q000494:pharmacology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D014407:Tumor Cells, Cultured; D051025:bcl-Associated Death Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D000964:Antimetabolites, Antineoplastic; C494819:BAD protein, human; D014408:Biomarkers, Tumor; D035683:MicroRNAs; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051025:bcl-Associated Death Protein; D005472:Fluorouracil
keywords: Apoptosis; BAD; BART miRNA; Cell proliferation; Epstein–Barr virus