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Published in: BMC Ophthalmology 1/2017

Open Access 01-12-2017 | Research article

MiRNAs regulate oxidative stress related genes via binding to the 3′ UTR and TATA-box regions: a new hypothesis for cataract pathogenesis

Authors: Changrui Wu, Zhao Liu, Le Ma, Cheng Pei, Li Qin, Ning Gao, Jun Li, Yue Yin

Published in: BMC Ophthalmology | Issue 1/2017

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Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.
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Metadata
Title
MiRNAs regulate oxidative stress related genes via binding to the 3′ UTR and TATA-box regions: a new hypothesis for cataract pathogenesis
Authors
Changrui Wu
Zhao Liu
Le Ma
Cheng Pei
Li Qin
Ning Gao
Jun Li
Yue Yin
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Ophthalmology / Issue 1/2017
Electronic ISSN: 1471-2415
DOI
https://doi.org/10.1186/s12886-017-0537-9

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