title: MiR-34a, a promising novel biomarker for benzene toxicity, is involved in cell apoptosis triggered by 1,4-benzoquinone through targeting Bcl-2.
abstract: Exposure to benzene is inevitable, and concerns regarding the adverse health effects of benzene have been raised. Most investigators found that benzene exposure induced hematotoxicity. In this regard, Our study aimed to explore a novel potential biomarker of adverse health effects following benzene exposure and the toxic mechanisms of benzene metabolites in vitro. This study consisted of 314 benzene-exposed workers and 288 control workers, an air benzene concentration of who were 2.64 ± 1.60 mg/m3and 0.05 ± 0.01 mg/m3, respectively. In this population-based study, miR-34a expression was elevated in benzene-exposed workers. The correlation of miR-34a with the airborne benzene concentration, S-phenylmercapturic acid (S-PMA) and trans, trans-muconic acid (t, t-MA), all of which reflect benzene exposure, was found. Correlation analysis indicated that miR-34a was associated with peripheral blood count, alanine transaminase (ALT) and oxidative stress. Furthermore, multivariate analysis demonstrated that miR-34a expression was strongly associated with white blood cell count (structure loadings = 0.952). In population-based study, miR-34a had the largest contribution to altered peripheral blood counts, which reflect benzene-induced hematotoxicity. The role of miR-34a in benzene toxicity was assessed using lentiviral vector transfection. Results revealed that 1,4-benzoquinone induced abnormal cell apoptosis and simultaneously upregulated miR-34a accompanied with decreased Bcl-2. Finally, inhibition of miR-34a elevated Bcl-2 and decreased 1,4-benzoquinone-induced apoptosis. In conclusion, miR-34a was observed to be involved in benzene-induced hematotoxicity by targeting Bcl-2 and could be regarded as a potential novel biomarker for benzene toxicity.
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: Xiaoli
authors.initials: X
authors.lastname: Guo
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: D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000633:toxicity; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D001554:Benzene / Q000633:toxicity*; D016227:Benzoquinones / Q000633:toxicity*; D015415:Biomarkers / Q000378:metabolism; D019254:Genes, bcl-2; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D013011:Sorbic Acid / Q000031:analogs & derivatives / Q000633:toxicity; D015854:Up-Regulation
chemical_list: D016227:Benzoquinones; D015415:Biomarkers; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; C005939:muconic acid; C004532:quinone; C053003:S-phenyl-N-acetylcysteine; D001554:Benzene; D000111:Acetylcysteine; D013011:Sorbic Acid
keywords: Apoptosis; Bcl-2; Benzene; Biomarker; MiR-34a