Ding Lu, Liu Jing, Shen Huan-Xi, Pan Li-Ping, Liu Qing-Dong, Zhang Heng-Dong, Han Lei, Shuai Li-Guo, Ding En-Min, Zhao Qiu-Ni, Wang Bo-Shen, Zhu Bao-Li
Suzhou Municipal Center for Disease Prevention and Control, Suzhou, Jiangsu, China.
Department of Occupational and Environmental Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
Hear Res. 2016 Mar;333:275-282. doi: 10.1016/j.heares.2015.08.003. Epub 2015 Aug 13.
Circulating microRNAs (miRNAs) have attracted interests as non-invasive biomarkers of physiological and pathological conditions, which may be applied in noise-induced hearing loss (NIHL). However, no epidemiology studies have yet examined the potential effects of NIHL or noise exposure on miRNA expression profiles.
We sought to identify permanent NIHL-related miRNAs and to predict the biological functions of the putative genes encoding the indicated miRNAs.
In the discovery stage, we used a microarray assay to detect the miRNA expression profiles between pooled plasma samples from 10 noise-exposed individuals with normal hearing and 10 NIHL patients. In addition, we conducted a preliminary validation of six candidate miRNAs in the same 20 workers. Subsequently, three miRNAs were selected for expanded validation in 23 non-exposed individuals with normal hearing and 46 noise-exposed textile workers which including 23 noise-exposed workers with normal hearing and 23 NIHL patients. Moreover, we predicted the biological functions of the putative target genes using a Gene Ontology (GO) function enrichment analysis.
In the discovery stage, compared with the noise exposures with normal hearing, 73 miRNAs demonstrated at least a 1.5-fold differential expression in the NIHL patients. In the preliminary validation, compared with the noise exposures, the plasma levels of miR-16-5p, miR-24-3p, miR-185-5p and miR-451a were all upregulated (P < 0.001) in the NIHL patients. In the expanded validation stage, compared with the non-exposures, the plasma levels of miR-24, miR-185-5p and miR-451a were all significantly downregulated (P < 0.001) in the exposures. And compared with the noise exposures, the plasma levels of miR-185-5p and miR-451a were slightly elevated (P < 0.001) in the NIHL patients, which were consistent with the results of preliminary validation and microarray analysis.
The two indicated plasma miRNAs may be biomarkers of indicating responses to noise exposure. However, further studies are necessary to prove the causal association between miRNAs changes and noise exposure, and to determine whether these two miRNAs are clear biomarkers to noise exposure.
循环微RNA(miRNA)作为生理和病理状况的非侵入性生物标志物已引起关注,其可能应用于噪声性听力损失(NIHL)。然而,尚无流行病学研究考察NIHL或噪声暴露对miRNA表达谱的潜在影响。
我们试图鉴定与永久性NIHL相关的miRNA,并预测编码所指示miRNA的假定基因的生物学功能。
在发现阶段,我们使用微阵列分析检测了10名听力正常的噪声暴露个体和10名NIHL患者的混合血浆样本之间的miRNA表达谱。此外,我们在相同的20名工人中对6种候选miRNA进行了初步验证。随后,选择3种miRNA在23名听力正常的非暴露个体和46名噪声暴露的纺织工人(包括23名听力正常的噪声暴露工人和23名NIHL患者)中进行扩大验证。此外,我们使用基因本体(GO)功能富集分析预测了假定靶基因的生物学功能。
在发现阶段,与听力正常的噪声暴露个体相比,73种miRNA在NIHL患者中表现出至少1.5倍的差异表达。在初步验证中,与噪声暴露个体相比,NIHL患者中miR-16-5p、miR-24-3p、miR-185-5p和miR-451a的血浆水平均上调(P < 0.001)。在扩大验证阶段,与非暴露个体相比,暴露个体中miR-24、miR-185-5p和miR-451a的血浆水平均显著下调(P < 0.001)。并且与噪声暴露个体相比,NIHL患者中miR-185-5p和miR-451a的血浆水平略有升高(P < 0.001),这与初步验证和微阵列分析的结果一致。
所指示的两种血浆miRNA可能是指示对噪声暴露反应的生物标志物。然而,需要进一步研究来证明miRNA变化与噪声暴露之间的因果关系,并确定这两种miRNA是否为明确的噪声暴露生物标志物。