title: MiR-133a regarded as a potential biomarker for benzene toxicity through targeting Caspase-9 to inhibit apoptosis induced by benzene metabolite (1,4-Benzoquinone).
abstract: Benzene is an environmental and industrial chemical which is widely utilized in various applications. Our previous study showed that miR-133a expression was down-regulated in chronic benzene poisoning workers, but the mechanism of miR-133a in benzene-induced hematotoxicity remains unclear. In this population-based study, benzene-exposed group recruited workers whose concentration of air benzene was 3.50±1.60mg/m(3), and control workers who were exposed to 0.06±0.01mg/m(3) air benzene. By comparison, Caspase-9 and Caspase-3 was up-regulated while miR-133a expression decreased in benzene-exposed workers. Pearson correlation analysis showed that miR-133a was reversely correlated with pro-apoptotic gene Caspase-9 in population-based study. Moreover, multiple linear regressions indicated that miR-133a was positively associated with blood cells count. To explore the underlying mechanism of miR-133a in benzene-induced hematotoxicity, AO/EB staining and TEM ultrastructural analysis were conducted to verify the activation of apoptosis in Human Leukemic U937 Cells induced by benzene metabolites (1,4-Benzoquinone, 1,4-BQ), while the mechanism of miR-133a in 1,4-BQ-induced apoptosis was performed using lentivirus vectors transfection. The results demonstrated that 1,4-BQ evidently induced mitochondria-mediated apoptosis and increased pro-apoptotic genes (Caspase-9 and Caspase-3) expression in a dose-dependent manner. The mechanistic study showed 1,4-BQ decreased miR-133a expression and miR-133a over-expression attenuated 1, 4-BQ-caused upregulation of Caspase-9, Caspase-3 and apoptosis. In conclusion, our research suggested that benzene induced hematotoxicity by decreasing miR-133a and caspase-dependent apoptosis which might contribute to the underlying mechanism of miR-133a in benzene-induced hematotoxicity.
authors.affiliation: Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors.forename: Yujiao
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, 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 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors.forename: Wenlin
authors.initials: W
authors.lastname: Bai
authors.affiliation: Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China. Electronic address: gaoai0980@163.com.
authors.forename: Ai
authors.initials: A
authors.lastname: Gao
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001554:Benzene / Q000378:metabolism / Q000633:toxicity*; D016227:Benzoquinones / Q000378:metabolism / Q000633:toxicity; D053148:Caspase 3 / Q000235:genetics* / Q000378:metabolism; D053453:Caspase 9 / Q000235:genetics* / Q000378:metabolism; D000074062:Environmental Biomarkers; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism; D020298:U937 Cells; D015854:Up-Regulation
chemical_list: D016227:Benzoquinones; D000074062:Environmental Biomarkers; C548234:MIRN133 microRNA, human; D035683:MicroRNAs; C004532:quinone; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D001554:Benzene
keywords: Apoptosis; Benzene; Biomarker; Caspase-9; miR-133a