NMI, POLR3G and APIP are the key molecules connecting glaucoma with high intraocular pressure: a clue for early diagnostic biomarker candidates.

IF 1.9 4区 医学 Q2 OPHTHALMOLOGY International journal of ophthalmology Pub Date : 2024-11-18 eCollection Date: 2024-01-01 DOI:10.18240/ijo.2024.11.03
Nawaf Almarzouki
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Abstract

Aim: To understand the molecular connectivity between the intraocular pressure (IOP) and glaucoma which will provide possible clues for biomarker candidates.

Methods: The current study uncovers the important genes connecting IOP with the core functional modules of glaucoma. An integrated analysis was performed using glaucoma and IOP microarray datasets to screen for differentially expressed genes (DEGs) in both conditions. To the selected DEGs, the protein interaction network was constructed and dissected to determine the core functional clusters of glaucoma. For the clusters, the connectivity of IOP DEGs was determined. Further, enrichment analyses were performed to assess the functional annotation and potential pathways of the crucial clusters.

Results: The gene expression analysis of glaucoma and IOP with normal control showed that 408 DEGs (277 glaucoma and 131 IOP genes) were discovered from two GEO datasets. The 290 DEGs of glaucoma were extended to form a network containing 1495 proteins with 9462 edges. Using ClusterONE, the network was dissected to have 12 clusters. Among them, three clusters were linked with three IOP DEGs [N-Myc and STAT Interactor (NMI), POLR3G (RNA Polymerase III Subunit G), and APAF1-interacting protein (APIP)]. In the clusters, ontology analysis revealed that RNA processing and transport, p53 class mediators resulting in cell cycle arrest, cellular response to cytokine stimulus, regulation of phosphorylation, regulation of type I interferon production, DNA deamination, and cellular response to hypoxia were significantly enriched to be implicated in the development of glaucoma. Finally, NMI, POLR3G, and APIP may have roles that were noticed altered in glaucoma and IOP conditions.

Conclusion: Our findings could help to discover new potential biomarkers, elucidate the underlying pathophysiology, and identify new therapeutic targets for glaucoma.

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NMI、POLR3G 和 APIP 是连接青光眼和高眼压的关键分子:早期诊断生物标记候选物的线索。
目的:了解眼压与青光眼之间的分子联系,为候选生物标志物提供可能的线索:目前的研究发现了连接眼压与青光眼核心功能模块的重要基因。利用青光眼和眼压微阵列数据集进行综合分析,筛选两种情况下的差异表达基因(DEGs)。针对筛选出的 DEGs,构建并剖析了蛋白质相互作用网络,以确定青光眼的核心功能集群。对于这些集群,还确定了眼压 DEGs 的连接性。此外,还进行了富集分析,以评估关键集群的功能注释和潜在通路:青光眼和眼压与正常对照的基因表达分析表明,从两个 GEO 数据集中发现了 408 个 DEGs(277 个青光眼基因和 131 个眼压基因)。青光眼的 290 个 DEGs 被扩展成一个包含 1495 个蛋白质、9462 条边的网络。使用 ClusterONE,该网络被分解为 12 个聚类。其中,3 个聚类与 3 个眼压 DEGs [N-Myc and STAT Interactor (NMI)、POLR3G (RNA Polymerase III Subunit G) 和 APAF1-interacting protein (APIP)] 相关联。本体分析表明,RNA加工和转运、导致细胞周期停滞的p53类介导因子、细胞对细胞因子刺激的反应、磷酸化调控、I型干扰素产生的调控、DNA脱氨以及细胞对缺氧的反应等与青光眼的发生发展有显著的关联。最后,NMI、POLR3G 和 APIP 的作用可能在青光眼和眼压条件下发生了明显改变:我们的发现有助于发现新的潜在生物标志物,阐明潜在的病理生理学,并确定新的青光眼治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
2.50
自引率
7.10%
发文量
3141
审稿时长
4-8 weeks
期刊介绍: · International Journal of Ophthalmology-IJO (English edition) is a global ophthalmological scientific publication and a peer-reviewed open access periodical (ISSN 2222-3959 print, ISSN 2227-4898 online). This journal is sponsored by Chinese Medical Association Xi’an Branch and obtains guidance and support from WHO and ICO (International Council of Ophthalmology). It has been indexed in SCIE, PubMed, PubMed-Central, Chemical Abstracts, Scopus, EMBASE , and DOAJ. IJO JCR IF in 2017 is 1.166. IJO was established in 2008, with editorial office in Xi’an, China. It is a monthly publication. General Scientific Advisors include Prof. Hugh Taylor (President of ICO); Prof.Bruce Spivey (Immediate Past President of ICO); Prof.Mark Tso (Ex-Vice President of ICO) and Prof.Daiming Fan (Academician and Vice President, Chinese Academy of Engineering. International Scientific Advisors include Prof. Serge Resnikoff (WHO Senior Speciatist for Prevention of blindness), Prof. Chi-Chao Chan (National Eye Institute, USA) and Prof. Richard L Abbott (Ex-President of AAO/PAAO) et al. Honorary Editors-in-Chief: Prof. Li-Xin Xie(Academician of Chinese Academy of Engineering/Honorary President of Chinese Ophthalmological Society); Prof. Dennis Lam (President of APAO) and Prof. Xiao-Xin Li (Ex-President of Chinese Ophthalmological Society). Chief Editor: Prof. Xiu-Wen Hu (President of IJO Press). Editors-in-Chief: Prof. Yan-Nian Hui (Ex-Director, Eye Institute of Chinese PLA) and Prof. George Chiou (Founding chief editor of Journal of Ocular Pharmacology & Therapeutics). Associate Editors-in-Chief include: Prof. Ning-Li Wang (President Elect of APAO); Prof. Ke Yao (President of Chinese Ophthalmological Society) ; Prof.William Smiddy (Bascom Palmer Eye instituteUSA) ; Prof.Joel Schuman (President of Association of University Professors of Ophthalmology,USA); Prof.Yizhi Liu (Vice President of Chinese Ophtlalmology Society); Prof.Yu-Sheng Wang (Director of Eye Institute of Chinese PLA); Prof.Ling-Yun Cheng (Director of Ocular Pharmacology, Shiley Eye Center, USA). IJO accepts contributions in English from all over the world. It includes mainly original articles and review articles, both basic and clinical papers. Instruction is Welcome Contribution is Welcome Citation is Welcome Cooperation organization International Council of Ophthalmology(ICO), PubMed, PMC, American Academy of Ophthalmology, Asia-Pacific, Thomson Reuters, The Charlesworth Group, Crossref,Scopus,Publons, DOAJ etc.
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