Discrepant Expression of MicroRNAs in Transparent and Cataractous Human Lenses

Discrepant Expression of MicroRNAs in Transparent and Cataractous Human Lenses
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透明和白内障人类晶状体中 MicroRNA 的表达差异

DOI:
10.1167/iovs.11-9178
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发表时间:
2012-06-01
影响因子:
4.4
通讯作者:
Zhang, Hui
Zhang, Hui
中科院分区:
医学2区
文献类型:
--
作者:
Wu, Changrui;Lin, Haotian;Zhang, Hui

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目的。年龄相关性白内障被认为是随着衰老的进展而出现的一种病理状况。然而,人们对microRNAs (miRNAs)在老年性白内障形成中的作用知之甚少。本研究的目的是确定透明和年龄相关性白内障晶状体中央上皮中miRNA表达的可能差异。采用微阵列技术测定透明晶状体和白内障晶状体的miRNA表达谱。通过微阵列软件对结果进行显著性分析,并通过茎环RT-PCR对结果进行验证。使用算法预测差异表达的mirna的靶基因。在所有人类晶状体中鉴定出了256个mirna。透明镜片中按表达水平排名前8位的mirna分别是miR-184、let-7b、miR-923、miR-1826、miR-125b、miR-1308、miR-26a和miR-638。相比之下,白内障晶状体中排名前八的mirna分别是miR-184、miR-1826、let-7b/c、miR-24、miR-23b、miR-923和miR-23a。与白内障晶状体相比,透明晶状体中有20种mirna表达水平升高,其中12种mirna表达水平降低2倍以上。茎环RT-PCR证实了这些发现。此外,据报道,一些被预测为已鉴定mirna靶点的基因参与了晶状体发育或白内障的形成。作者首次报道了透明和年龄相关性白内障晶状体中央上皮中miRNAs的独特表达谱。发现了miRNA表达的显著差异,并预测了相关miRNA靶向的基因。miRNAs的差异表达表明这些miRNAs在晶状体发育和/或白内障形成中具有潜在的作用。(Invest Ophthalmol Vis Sci. 2012;53:3906-3912) DOI:10.1167/iovs.11-9178
PURPOSE. Age-related cataracts are considered to be a pathological condition that arise as senescence progresses. However, little is known about the function of microRNAs (miRNAs) in the formation of age-related cataracts. The purpose of this study was to identify possible differences in miRNA expression in the central epithelium of transparent and age-related cataractous human lenses.METHODS. Microarrays were used to determine the miRNA expression profiles of both transparent and cataractous lenses. The results were analyzed by significance analyses performed by the microarray software, and the results were confirmed by stem-loop RT-PCR. Algorithms were used to predict the target genes of the differentially expressed miRNAs.RESULTS. Two hundred and six miRNAs were identified in all human lenses. The top eight miRNAs according to expression levels were miR-184, let-7b, miR-923, miR-1826, miR-125b, miR-1308, miR-26a, and miR-638 in transparent lenses. In contrast, the top eight miRNAs in cataractous lenses were miR-184, miR-1826, let-7b/c, miR-24, miR-23b, miR-923, and miR-23a. The expression levels of 20 miRNAs were increased and the levels of 12 miRNAs were decreased by more than 2-fold in transparent lenses relative to the levels in cataractous lenses. These findings were confirmed by stem-loop RT-PCR. In addition, several genes that were predicted to be targets of the identified miRNAs have been reported to be involved in lens development or cataract formation.CONCLUSIONS. The authors report, for the first time, the distinct expression profiles of miRNAs in the central epithelium of transparent and age-related cataractous human lenses. Significant differences in miRNA expression were identified, and the genes targeted by the relevant miRNAs were predicted. The differential expression of miRNAs suggests that these miRNAs have potential roles in lens development and/or cataract formation. (Invest Ophthalmol Vis Sci. 2012;53:3906-3912) DOI:10.1167/iovs.11-9178