Liu Yang, Chen Xianwen, Bian Qian, Shi Yuan, Liu Qingdong, Ding Lu, Zhang Hengdong, Zhu Baoli
1 Jiangyin Municipal Center for Disease Prevention and Control, Wuxi, China ; 2 Jiangsu Provincial Center for Disease Prevention and Control, Nanjing 210009, China ; 3 School of Public Health, Southeast University, Nanjing, China ; 4 Suzhou Municipal Center for Disease Prevention and Control, Suzhou, China.
J Thorac Dis. 2016 Mar;8(3):403-14. doi: 10.21037/jtd.2016.02.56.
Circulating microRNA (miRNA) has attractive interests as a non-invasive biomarker of physiological and pathological conditions. Our study aimed to investigate the potential effects of chronic benzene poisoning (CBP) and benzene exposure on miRNA expression, and identify CBP-related miRNAs.
In the discovery stage, we used a microarray assay to detect the miRNA expression profiles among pooled plasma samples from ten CBP patients, ten healthy benzene-exposed individuals and ten non-benzene exposed individuals. Subsequently, we conducted an expanded validation of six candidate miRNAs in 27 CBP patients- low blood counts, 54 healthy benzene-exposed individuals and 54 non-exposed individuals. Moreover, we predicted the biological functions of putative target genes using a Gene Ontology (GO) function enrichment analysis and KEGG pathway analysis.
In the discovery stage, compared with non-exposures, 36 and 12 miRNAs demonstrated at least a 1.0-fold differential expression in the CBP patients and the benzene exposures, respectively. And compared with benzene exposures, 58 miRNAs demonstrated at least a 1.0-fold differential expression in the CBP patients. In the expanded validation stage, compared with non-exposures as well as exposures, miR-24-3p and miR-221-3p were significantly up-regulated (1.99- and 2.06-fold for miR-24-3p, 2.19- and 3.93-fold for miR-221-3p, P<0.01) while miR-122-5p and miR-638 were significantly down-regulated (-3.45- and -2.60-fold for miR-122-5p, -1.82- and -3.20-fold for miR-638, P<0.001) in the CBP patients; compared with non-exposures, the plasma level of miR-638 was significantly up-regulated (1.38-fold, P<0.01) while the plasma levels miR-122-5p and miR-221-3p were significantly down-regulated (-0.85- and -1.74-fold, P<0.01) in the exposures, which were consistent with the results of microarray analysis.
The four indicated plasma miRNAs may be biomarkers of indicating responses to benzene exposure. Further studies are warranted to verify our findings with a large sample and to confirm the underlying mechanisms.
循环微RNA（miRNA）作为生理和病理状况的非侵入性生物标志物具有极大的研究价值。我们的研究旨在探讨慢性苯中毒（CBP）和苯暴露对miRNA表达的潜在影响，并鉴定与CBP相关的miRNA。
在发现阶段，我们使用微阵列分析检测了来自10名CBP患者、10名健康苯暴露个体和10名非苯暴露个体的混合血浆样本中的miRNA表达谱。随后，我们在27名CBP患者（低血细胞计数）、54名健康苯暴露个体和54名非暴露个体中对6种候选miRNA进行了扩大验证。此外，我们使用基因本体（GO）功能富集分析和KEGG通路分析预测了假定靶基因的生物学功能。
在发现阶段，与非暴露组相比，分别有36种和12种miRNA在CBP患者和苯暴露个体中表现出至少1.0倍的差异表达。与苯暴露组相比，有58种miRNA在CBP患者中表现出至少1.0倍的差异表达。在扩大验证阶段，与非暴露组以及暴露组相比，CBP患者中miR-24-3p和miR-221-3p显著上调（miR-24-3p分别上调1.99倍和2.06倍，miR-221-3p分别上调2.19倍和3.93倍，P<0.01），而miR-122-5p和miR-638显著下调（miR-122-5p分别下调3.45倍和2.60倍，miR-638分别下调1.82倍和3.20倍，P<0.001）；与非暴露组相比，暴露组中miR-638的血浆水平显著上调（1.38倍，P<0.01），而miR-122-5p和miR-221-3p的血浆水平显著下调（分别下调0.85倍和1.74倍，P<0.01），这与微阵列分析结果一致。
所指出的四种血浆miRNA可能是指示对苯暴露反应的生物标志物。有必要进一步开展研究，以大样本验证我们的发现并确认潜在机制。
