MiRNAs regulate oxidative stress related genes via binding to the 3' UTR and TATA-box regions: a new hypothesis for cataract pathogenesis.
MiRNAs regulate oxidative stress related genes via binding to the 3' UTR and TATA-box regions: a new hypothesis for cataract pathogenesis.
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DOI：
10.1186/s12886-017-0537-9
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发表时间：
2017-08-14
影响因子：
2
通讯作者：
Yin Y
中科院分区：
文献类型：
--
作者：
Wu C;Liu Z;Ma L;Pei C;Qin L;Gao N;Li J;Yin Y
年龄相关性白内障与氧化应激有关。然而，白内障相关氧化应激相关基因的全基因组筛选尚未得到彻底研究。我们的研究旨在鉴定与氧化应激相关的白内障调控 miRNA 靶基因，并提出白内障形成的新可能机制。微阵列用于确定透明晶状体和白内障晶状体的 mRNA 表达谱。通过微阵列软件对结果进行显着性分析，并使用分子注释系统进一步进行生物信息学分析。真核启动子数据库 (EPD) 用于检索启动子序列并鉴定 TATA-box 基序。利用在线资源 miRWalk 来筛选针对与氧化应激相关的 mRNA 的经过验证的 miRNA。应用 RNAhybrid 在线工具来预测白内障晶状体中显着调节的 miRNA 与目标 mRNA 之间的结合。白内障晶状体样本中的氧化应激途径受到显着调节。促氧化基因有一半上调（11/20），少数基因下调（4/20），其余基因没有显着变化（5/20）。抗氧化基因部分上调（17/69），部分下调（17/69）。四个下调的 miRNA（has-miR-1207-5p、has-miR-124-3p、has-miR-204-3p、has-miR-204-5p）被发现可靶向促氧化基因的 3' UTR，并且还可以结合抗氧化基因的 TATA-box 区域（has-miR-204-3p 除外），而两个上调的 miRNA （has-miR-222-3p、has-miR-378a-3p）被发现以抗氧化基因的 3' UTR 为靶点，并且可以同时与促氧化基因的 TATA-box 区域结合。我们首次提出这样的假设：白内障调节的 miRNA 不仅可以通过靶向 3'UTR，还可以通过靶向氧化应激相关基因的 TATA-box 区域来促进白内障形成。这导致随后促氧化基因的升高和抗氧化基因的抑制。这种 miRNA-TATA-box/3' UTR 基因调控网络可能有助于白内障发病机制。本文的在线版本 (doi:10.1186/s12886-017-0537-9) 包含补充材料，可供授权用户使用。
Age-related cataracts are related to oxidative stress. However, the genome-wide screening of cataract related oxidative stress related genes are not thoroughly investigated. Our study aims to identify cataract regulated miRNA target genes that are related to oxidative stress and to propose a new possible mechanism for cataract formation. Microarrays were used to determine the mRNA expression profiles of both transparent and cataractous lenses. The results were analyzed by significance analyses performed by the microarray software, and bioinformatics analysis was further conducted using Molecular Annotation System. The Eukaryotic Promoter Database (EPD) was used to retrieve promoter sequences and identify TATA-box motifs. Online resource miRWalk was exploited to screen for validated miRNAs targeting mRNAs related to oxidative stress. RNAhybrid online tool was applied to predict the binding between significantly regulated miRNAs in cataract lenses and target mRNAs. Oxidative stress pathway was significantly regulated in cataractous lens samples. Pro-oxidative genes were half up-regulated (11/20), with a small number of genes down-regulated (4/20) and the rest of them with no significant change (5/20). Anti-oxidative genes were partly up-regulated (17/69) and partly down-regulated (17/69). Four down-regulated miRNAs (has-miR-1207-5p, has-miR-124-3p, has-miR-204-3p, has-miR-204-5p) were found to target 3′ UTR of pro-oxidative genes and could also bind to the TATA-box regions of anti-oxidative genes (with the exception of has-miR-204-3p), whilst two up-regulated miRNAs (has-miR-222-3p, has-miR-378a-3p) were found to target 3′ UTR of anti-oxidative genes and could simultaneously bind to the TATA-box regions of pro-oxidative genes. We propose for the first time a hypothesis that cataract regulated miRNAs could contribute to cataract formation not only by targeting 3′ UTR but also by targeting TATA-box region of oxidative stress related genes. This results in the subsequent elevation of pro-oxidative genes and inhibition of anti-oxidative genes. This miRNA-TATA-box/3′ UTR-gene-regulation network may contribute to cataract pathogenesis. The online version of this article (doi:10.1186/s12886-017-0537-9) contains supplementary material, which is available to authorized users.
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影响因子：
14.9
作者：
Dreos R;Ambrosini G;Cavin Périer R;Bucher P
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