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与燃煤型砷中毒相关的循环微RNA及其靶基因

Circulating miRNAs and their target genes associated with arsenism caused by coal-burning.

作者信息

Sun Baofei, Xue Junchao, Li Jun, Luo Fei, Chen Xiong, Liu Yonglian, Wang Qingling, Qi Caihua, Zou Zhonglan, Zhang Aihua, Liu Qizhan

机构信息

Key Laboratory of Environmental Pollution Monitoring and Disease Control , Ministry of Education , Department of Toxicology , School of Public Health , Guizhou Medical University , Guiyang 550025 , Guizhou , China . Email:

Institute of Toxicology , School of Public Health , Nanjing Medical University , Nanjing 211166 , Jiangsu , China . Email:

出版信息

Toxicol Res (Camb). 2017 Jan 23;6(2):162-172. doi: 10.1039/c6tx00428h. eCollection 2017 Mar 1.

Abstract

Endemic arsenism, caused by burning coal containing high levels of arsenic, is found only in the Guizhou and Shanxi Provinces of China. Dysregulated microRNAs (miRNAs), detected in the blood, are emerging as promising biomarkers. At present, little is known about the change and clinical efficacy of circulating miRNAs in patients with endemic arsenism produced by burning of coal. Here, we determined, by using TaqMan Human miRNA Array Chips, the differential expression of plasma miRNAs between patients with arsenism caused by coal-burning and a control group. Four increased miRNAs (miR-21, miR-145, miR-155, and miR-191) were verified in a larger sample by quantitative real-time PCR. Furthermore, bioinformatics and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to associate changes in plasma levels of the miRNAs with their functions and their effects on various pathways. The results of chip array assays show that the levels of miR-21, miR-141, miR-148a, miR-145, miR-155, miR-191, miR-218, and miR-491 were most prominently increased and that the levels of miR-200b, miR-200c, miR-26, and miR-34c were decreased. The qRT-PCR results confirm that the circulating levels of miR-21, miR-145, miR-155, and miR-191 are increased in patients with arsenism caused by coal-burning. KEGG analyses show that these miRNAs inhibit the target genes of pathways related to immune inflammation, oxidative stress, and DNA damage repair. Therefore, the four miRNAs may be biomarkers of endemic arsenism caused by coal-burning. Further studies with larger samples should be performed to confirm these findings and to elucidate the underlying mechanisms.

摘要

燃煤型地方性砷中毒仅在中国贵州省和山西省被发现,它是由燃烧高砷煤所致。血液中检测到的失调微小RNA(miRNA)正成为有前景的生物标志物。目前,对于燃煤型地方性砷中毒患者循环miRNA的变化及临床疗效知之甚少。在此,我们使用TaqMan人类miRNA阵列芯片,测定了燃煤型砷中毒患者与对照组血浆miRNA的差异表达。通过定量实时PCR在更大样本中验证了4种上调的miRNA(miR-21、miR-145、miR-155和miR-191)。此外,利用生物信息学和京都基因与基因组百科全书(KEGG)通路富集分析,将miRNA血浆水平的变化与其功能以及对各种通路的影响相关联。芯片阵列分析结果显示,miR-21、miR-141、miR-148a、miR-145、miR-155、miR-191、miR-218和miR-491的水平显著升高,而miR-200b、miR-200c、miR-26和miR-34c的水平降低。qRT-PCR结果证实,燃煤型砷中毒患者中miR-21、miR-145、miR-155和miR-191的循环水平升高。KEGG分析表明,这些miRNA抑制与免疫炎症、氧化应激和DNA损伤修复相关通路的靶基因。因此,这4种miRNA可能是燃煤型地方性砷中毒的生物标志物。应进行更大样本的进一步研究以证实这些发现并阐明潜在机制。

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