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鉴定miR-671-5p及其相关通路作为小鼠形觉剥夺性近视和晶状体诱导性近视的共同机制

Identification of miR-671-5p and Its Related Pathways as General Mechanisms of Both Form-Deprivation and Lens-Induced Myopia in Mice.

作者信息

Cui Zedu, Huang Yuke, Chen Xi, Chen Taiwei, Hou Xiangtao, Yu Na, Li Yan, Qiu Jin, Chen Pei, Yu Keming, Zhuang Jing

机构信息

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.

Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, China.

出版信息

Curr Issues Mol Biol. 2023 Mar 2;45(3):2060-2072. doi: 10.3390/cimb45030132.

Abstract

Animal models have been indispensable in shaping the understanding of myopia mechanisms, with form-deprivation myopia (FDM) and lens-induced myopia (LIM) being the most utilized. Similar pathological outcomes suggest that these two models are under the control of shared mechanisms. miRNAs play an important role in pathological development. Herein, based on two miRNA datasets (GSE131831 and GSE84220), we aimed to reveal the general miRNA changes involved in myopia development. After a comparison of the differentially expressed miRNAs, miR-671-5p was identified as the common downregulated miRNA in the retina. miR-671-5p is highly conserved and related to 40.78% of the target genes of all downregulated miRNAs. Moreover, 584 target genes of miR-671-5p are related to myopia, from which we further identified 8 hub genes. Pathway analysis showed that these hub genes are enriched in visual learning and extra-nuclear estrogen signaling. Furthermore, two of the hub genes are also targeted by atropine, which strongly supports a key role of miR-671-5p in myopic development. Finally, Tead1 was identified as a possible upstream regulator of miR-671-5p in myopia development. Overall, our study identified the general regulatory role of miR-671-5p in myopia as well as its upstream and downstream mechanisms and provided novel treatment targets, which might inspire future studies.

摘要

动物模型在塑造对近视机制的理解方面一直不可或缺,其中形觉剥夺性近视(FDM)和晶状体诱导性近视(LIM)是最常用的。相似的病理结果表明这两种模型受共同机制的控制。微小RNA(miRNA)在病理发展中起重要作用。在此,基于两个miRNA数据集(GSE131831和GSE84220),我们旨在揭示近视发展过程中普遍存在的miRNA变化。在比较差异表达的miRNA后,miR-671-5p被确定为视网膜中共同下调的miRNA。miR-671-5p高度保守,与所有下调miRNA的40.78%的靶基因相关。此外,miR-671-5p的584个靶基因与近视相关,我们从中进一步鉴定出8个核心基因。通路分析表明这些核心基因在视觉学习和核外雌激素信号传导中富集。此外,其中两个核心基因也是阿托品的作用靶点,这有力地支持了miR-671-5p在近视发展中的关键作用。最后,Tead1被确定为近视发展中miR-671-5p可能的上游调节因子。总体而言,我们的研究确定了miR-671-5p在近视中的一般调节作用及其上下游机制,并提供了新的治疗靶点,这可能会启发未来的研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4bb/10047131/427425a5b404/cimb-45-00132-g001.jpg

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