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鉴定和分析眼外肌动眼神经麻痹差异表达的环状 RNA。

Identification and characterization of differentially expressed circular RNAs in extraocular muscle of oculomotor nerve palsy.

机构信息

Eye Institute, Department of Ophthalmology, Eye & ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai, 200031, China.

NHC Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Sciences, 83 Fenyang Road, Shanghai, 200031, China.

出版信息

BMC Genomics. 2023 Oct 17;24(1):617. doi: 10.1186/s12864-023-09733-3.

Abstract

BACKGROUND

Oculomotor nerve palsy (ONP) is a neuroparalytic disorder resulting in dysfunction of innervating extraocular muscles (EOMs), of which the pathological characteristics remain underexplored.

METHODS

In this study, medial rectus muscle tissue samples from four ONP patients and four constant exotropia (CXT) patients were collected for RNA sequencing. Differentially expressed circular RNAs (circRNAs) were identified and included in functional enrichment analysis, followed by interaction analysis with microRNAs and mRNAs as well as RNA binding proteins. Furthermore, RT-qPCR was used to validate the expression level of the differentially expressed circRNAs.

RESULTS

A total of 84 differentially expressed circRNAs were identified from 10,504 predicted circRNAs. Functional enrichment analysis indicated that the differentially expressed circRNAs significantly correlated with skeletal muscle contraction. In addition, interaction analyses showed that up-regulated circRNA_03628 was significantly interacted with RNA binding protein AGO2 and EIF4A3 as well as microRNA hsa-miR-188-5p and hsa-miR-4529-5p. The up-regulation of circRNA_03628 was validated by RT-qPCR, followed by further elaboration of the expression, location and clinical significance of circRNA_03628 in EOMs of ONP.

CONCLUSIONS

Our study may shed light on the role of differentially expressed circRNAs, especially circRNA_03628, in the pathological changes of EOMs in ONP.

摘要

背景

动眼神经麻痹(ONP)是一种神经麻痹性疾病,导致支配眼外肌(EOM)的功能障碍,其病理特征仍未得到充分探索。

方法

本研究收集了 4 名 ONP 患者和 4 名恒定性外斜视(CXT)患者的内直肌组织样本进行 RNA 测序。鉴定差异表达的环状 RNA(circRNA),并进行功能富集分析,然后与 microRNA 和 mRNA 以及 RNA 结合蛋白进行相互作用分析。此外,使用 RT-qPCR 验证差异表达 circRNA 的表达水平。

结果

从 10504 个预测的 circRNA 中鉴定出 84 个差异表达的 circRNA。功能富集分析表明,差异表达的 circRNA 与骨骼肌收缩显著相关。此外,相互作用分析表明,上调的 circRNA_03628 与 RNA 结合蛋白 AGO2 和 EIF4A3 以及 microRNA hsa-miR-188-5p 和 hsa-miR-4529-5p 显著相互作用。通过 RT-qPCR 验证了 circRNA_03628 的上调,随后进一步阐述了 circRNA_03628 在 ONP 眼外肌中的表达、位置和临床意义。

结论

我们的研究可能揭示差异表达的 circRNA,特别是 circRNA_03628,在 ONP 中 EOM 病理变化中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8d7/10583365/63aa1bc225f1/12864_2023_9733_Fig1_HTML.jpg

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