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.
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.
Exp Mol Pathol. 2014 Jun;96(3):426-30. doi: 10.1016/j.yexmp.2014.04.011. Epub 2014 Apr 26.
Chronic occupational benzene exposure is associated with an increased risk of hematological malignancies. To gain an insight into the new biomarkers and molecular mechanisms of chronic benzene poisoning, miRNA profiles and mRNA expression pattern from the peripheral blood mononuclear cells of chronic benzene poisoning patients and health controls matched age and gender without benzene exposure were performed using the Exiqon miRNA PCR ARRAY and Gene Chip Human Gene 2.0ST Arrays, respectively. Totally, 6 up-regulated miRNAs (miR-34a, miR-205, miR-10b, let-7d, miR-185 and miR-423-5p-2) and 7 down-regulated miRNAs (miR-133a, miR-543, hsa-miR-130a, miR-27b,miR-223, miR-142-5p and miR-320b) were found in chronic benzene poisoning group compared to health controls (P ≤ 0.05). By integrating miRNA and mRNA expression data, these differential miRNAs were mainly involved in regulation of transcription from RNA polymerase II promoter, axon guidance, regulation of transcription, DNA-dependent, nervous system development, and regulation of actin cytoskeleton organization. Further, pathway analysis indicated that SMAD4, PLCB1, NFAT5, GNAI2, PTEN, VEGFA, BCL2, CTNNB1 and CCND1 were key target genes of differential miRNAs which were implicated in Adherens junction, TGF-beta signaling pathway, Wnt signaling pathway, tight junction and Pathways in cancer. In conclusion, the aberrant miRNAs might be a potential biomarker of chronic benzene poisoning.
慢性职业性苯暴露与血液系统恶性肿瘤风险增加相关。为深入了解慢性苯中毒的新生物标志物和分子机制,本研究采用 Exiqon miRNA PCR ARRAY 和 GeneChip Human Gene 2.0ST Arrays,分别检测了慢性苯中毒患者和年龄、性别相匹配的无苯暴露健康对照者外周血单个核细胞中的 miRNA 谱和 mRNA 表达谱。结果发现,与健康对照者相比,慢性苯中毒组有 6 个上调 miRNA(miR-34a、miR-205、miR-10b、let-7d、miR-185 和 miR-423-5p-2)和 7 个下调 miRNA(miR-133a、miR-543、hsa-miR-130a、miR-27b、miR-223、miR-142-5p 和 miR-320b)(P ≤ 0.05)。通过整合 miRNA 和 mRNA 表达数据,这些差异 miRNA 主要参与 RNA 聚合酶 II 启动子转录的调节、轴突导向、转录调节、DNA 依赖性、神经系统发育以及肌动蛋白细胞骨架组织的调节。进一步的通路分析表明,差异 miRNA 的关键靶基因 SMAD4、PLCB1、NFAT5、GNAI2、PTEN、VEGFA、BCL2、CTNNB1 和 CCND1 参与了粘着连接、TGF-β信号通路、Wnt 信号通路、紧密连接和癌症通路。综上所述,异常表达的 miRNA 可能是慢性苯中毒的潜在生物标志物。