title: Benzene and its metabolite decreases cell proliferation via LncRNA-OBFC2A-mediated anti-proliferation effect involving NOTCH1 and KLF15.
abstract: LncRNA has been considered to play a crucial role in the progression of several diseases by affecting cell proliferation. However, its role in benzene toxicity remains unclear. Our study showed that the expression of lncRNA-OBFC2A increased accompanied with the change of cell proliferation related-genes in benzene-exposed workers. In vitro experiments, 1,4-Benzoquinone dose-dependently inhibited cell proliferation and simultaneously caused the decrease of NOTCH1 expression and the increase of KLF15 in AHH-1 cell lines. Meanwhile, 1, 4-Benzoquinone obviously increased the expression of lncRNA-OBFC2A, which was consistent with our previous population results. Therefore, we propose that lncRNA-OBFC2A is involved in benzene toxicity by regulating cell proliferation. Further, we successfully constructed a lentivirus model of interfering the expression of lncRNA-OBFC2A. After interfering lncRNA-OBFC2A, the cell proliferation inhibition and the expression of NOTCH1 and KLF15 induced by 1, 4-Benzoquinone were reversed. Subsequently, RNA fluorescence in situ Hybridization assay showed that lncRNA-OBFC2A was located in cell nuclei. These results suggest that benzene and its metabolite decreases cell proliferation via LncRNA-OBFC2A-mediated anti-proliferation effect involving NOTCH1 and KLF15. LncRNA-OBFC2A can be a potential biomarker for benzene toxicity.
authors.affiliation: Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, China.
authors.forename: Pengling
authors.initials: P
authors.lastname: Sun
authors.affiliation: Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, China.
authors.forename: Yujiao
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Key Laboratory of Chemical Safety and Health, National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China.
authors.forename: Caihong
authors.initials: C
authors.lastname: Xing
authors.affiliation: Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, China.
authors.forename: Ai
authors.initials: A
authors.lastname: Gao
mesh_terms: D001554:Benzene / Q000506:poisoning*; D016227:Benzoquinones / Q000506:poisoning; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D009784:Occupational Diseases / Q000097:blood / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D016273:Occupational Exposure; D062085:RNA, Long Noncoding / Q000096:biosynthesis / Q000235:genetics*; D051881:Receptor, Notch1 / Q000235:genetics*; D014162:Transfection
chemical_list: D016227:Benzoquinones; D015415:Biomarkers; C414172:KLF15 protein, human; D051741:Kruppel-Like Transcription Factors; C497761:NOTCH1 protein, human; D009687:Nuclear Proteins; D062085:RNA, Long Noncoding; D051881:Receptor, Notch1; D001554:Benzene
keywords: 1; 4-Benzoquinone; RNA fluorescence in situ Hybridization assay; cell proliferation; lncRNA